Biomarkers in pancreatic cancer
By detecting the specific miRNA expression levels in biological samples of pancreatic cancer patients, the problem of insufficient early diagnosis sensitivity and specificity of pancreatic ductal adenocarcinoma in the prior art is solved, and higher diagnostic accuracy is achieved.
Patent Information
- Application Number
- CN202380048643.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2022-07-08
- Filing Date
- 2023-06-09
- Publication Date
- 2025-02-07
AI Technical Summary
In the prior art, early diagnosis of pancreatic ductal adenocarcinoma (PDAC) has problems with insufficient sensitivity and specificity, especially in the poor performance of CA19-9 serum biomarkers in early detection.
By detecting specific RNA expression levels elevated relative to control in a patient's biological sample, including cell free and exosomal miRNAs, such as miR-30c-5p, miR-142-3p, miR-340-5p, miR-335- 5p, miR-23b-3p, etc., are used to diagnose and identify pancreatic cancer.
Improves the accuracy of early diagnosis of pancreatic cancer and provides a more robust and specific biomarker that can effectively identify PDAC patients with normal CA19-9 levels.
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Figure CN119403940A_ABST
Abstract
Description
[0001] CROSS-REFERENCE TO RELATED APPLICATIONS
[0002] This application claims the benefit of priority to U.S. application No. 63 / 359,270, filed on July 8, 2022, and U.S. application No. 63 / 351,212, filed on June 10, 2022, the disclosures of which are incorporated herein by reference in their entireties.
[0003] STATEMENT REGARDING RIGHTS TO INVENTS RESULTING FROM FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT
[0004] This invention was made with government support under Grant CA214254 awarded by the National Institutes of Health. The government has certain rights in this invention. Background Art
[0005] Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy. PDAC is a serious health problem with an increasing incidence and is projected to become the second leading cause of cancer-related death in the United States within the next decade. Under standard treatment strategies, surgical resection of localized tumors offers the only potential cure for this disease. Recent clinical findings have clearly established that surgery following modern adjuvant chemotherapy significantly improves patient outcomes, with median overall survival in PDAC patients ranging from 46 to 54 months. Unfortunately, however, fewer than 15%-20% of patients present with localized, resectable, and potentially curable tumors at initial diagnosis, while the remainder suffer from more advanced, unresectable, or metastatic disease. This is reflected in the fact that despite recent advances in treatment modalities, the five-year survival rate for PDAC patients has remained largely unchanged in recent decades.
[0006] One of the emerging themes in recent years is that early disease diagnosis offers a promising opportunity for timely intervention and subsequent improvement in the survival of patients with this deadly malignancy. To date, several blood-based biomarkers have been evaluated for their clinical usefulness for the early diagnosis of PDAC. Serum carbohydrate antigen 19-9 (CA19-9) remains the best-documented and most widely used serum biomarker in patients with PDAC. Although CA19-9 is commonly used to monitor disease progression and treatment response, it lacks satisfactory sensitivity or specificity for screening and early detection of patients with PDAC. Importantly, 15%-25% of patients with PDAC (including those in the early stages) often exhibit CA19-9 levels below 37 U / ml, which is considered normal. Furthermore, 5%-10% of the general population is Lewis antigen-negative, with no or low CA19-9 secretion. In light of these clinical challenges in the field, the present disclosure addresses the urgent need to develop robust alternative, preferably non-invasive, biomarkers for the early diagnosis of PDAC. Summary of the Invention
[0007] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the methods comprising administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, administering to the patient an image-based screening, surgically removing all or part of the pancreas from the patient, or a combination of two or more thereof; wherein a biological sample obtained from the patient comprises elevated expression levels of an RNA relative to a control; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR -217-5p, exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p , exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof. In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, or a combination of two or more thereof.
[0008] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the methods comprising: (i) detecting elevated expression levels of RNA in a biological sample obtained from the patient relative to a control, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-23b-3p. p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof; and (ii) administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, administering image-based screening to the patient, surgically removing all or part of the pancreas of the patient, or a combination of two or more thereof. In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, or a combination of two or more thereof.
[0009] Provided herein is a method for diagnosing a patient with pancreatic cancer, the method comprising detecting elevated expression levels of RNA relative to a control in a biological sample obtained from the patient, thereby diagnosing the patient with pancreatic cancer; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, exosomal ...23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-23b-3p, exosomal miR-23b-3p, exosomal miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-23b-3p, exosomal miR-23b-3 cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof. In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, or a combination of two or more thereof.
[0010] These and other embodiments of the disclosure are described herein. BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Figures 1A to 1D : Expression levels of identified cell-free and exosomal miRNA candidates for diagnosis of patients with early-stage PDAC obtained from whole-genome small RNA sequencing. Figure 1A to Figure 1B : Expression levels and representative heatmaps of candidate cf-miRNAs in patients with early-stage PDAC (stage I to II) compared with non-disease control samples. Figure 1C to Figure 1DFigure 3: Expression levels and representative heatmaps of candidate exo-miRNAs in patients with PDAC (stages I to II) compared to non-disease control samples. The miRNA expression profiles were z-normalized. (miRNA: microRNA; CPM: counts per million; FC: fold change; PDAC: pancreatic ductal adenocarcinoma (light blue) and non-disease control (dark blue)).
[0012] Figures 2A to 2D : Performance evaluation of a cell-free and exosomal miRNA biomarker panel in a clinical cohort by qRT-PCR. Statistically significant candidates upregulated in patients with PDAC compared to non-disease controls. Figure 2A : cf-miRNA and Figure 2B : Representative heatmap of exo-miRNAs. Figure 2C : ROC curve analysis of cf-miRNA, exo-miRNA or combined cf- and exo- panels in the training cohort. Figure 2D : Receiver operating characteristic (ROC) curve analysis of the cf-miRNA, exo-miRNA, and combined cf and exosome panels in the validation cohort. (Exo: exosome; miRNA: microRNA; qRT-PCR: quantitative reverse transcription polymerase chain reaction; cf: cell-free; AUC: area under the curve; ROC: receiver operating characteristic)
[0013] Figures 3A to 3D : Prioritization and performance evaluation of cell-free and exosomal miRNA biomarker panels in a clinical cohort. Figure 3A : ROC curve analysis of cf-miRNA, exo-miRNA, or combined sets of cf and exosomes in the training cohort. Figure 3B : ROC curve analysis of cf-miRNA, exo-miRNA, or combined cf and exosome panels in the validation cohort. Figure 3C : ROC curve analysis identifying early-stage (stages I and II) and advanced-stage (stages III and IV) PDAC patients relative to disease-free controls in the validation cohort. Figure 3D Risk score analysis of all staged PDAC patients and disease-free controls in the validation cohort. Receiver operating characteristic (ROC) curves are shown with 95% confidence intervals (CIs). (*p < 0.001; Exo: exosomes; miRNA: microRNA; cf: cell-free; AUC: area under the curve; TNM: tumor-node-metastasis; PDAC: pancreatic ductal adenocarcinoma; ROC: receiver operating characteristic)
[0014] Figures 4A to 4E : Performance evaluation of miRNA signatures in combination with CA19-9, and assessment of diagnostic potential by decision curve analysis and calibration curve analysis. Figure 4A: ROC analysis comparing the diagnostic performance between cf and exosome combined miRNA signatures and CA19-9 in all stages of PDAC patients. Figure 4B : ROC analysis comparing the diagnostic performance of cf and exosome combined miRNA signatures with CA19-9 in early-stage (stage I and II) PDAC patients. Figure 4C : Performance of combined cf and exosomal miRNA signatures in a cohort of 81 participants (22 with PDAC and 59 non-disease controls) presenting with CA19-9 levels less than 37 U / mL. Figure 4D : Decision curve analysis and evaluation of the performance of combined miRNA biomarker panels Figure 4E Calibration curve analysis to evaluate the performance of a combined miRNA biomarker panel. Receiver operating characteristic (ROC) curves are shown with 95% confidence intervals (CIs). (miRNA: microRNA; CA19-9: carbohydrate antigen 19-9; AUC: area under the curve; Exo: exosome; cf: cell-free; ROC: receiver operating characteristic; PDAC: pancreatic ductal adenocarcinoma)
[0015] Figure 5 A summary of the diagnostic performance of biomarker panels based on cell-free and exosomal miRNAs in training and validation cohorts is provided.
[0016] Figure 6 The diagnostic performance of CA19-9 alone and the miRNA signature in combination with CA19-9 after fixing their specificities at 95% and 99% are presented.
[0017] Figure 7 Clinicopathological characteristics of patients with pancreatic ductal adenocarcinoma and disease-free controls are shown.
[0018] Figure 8 A summary of the diagnostic performance of biomarkers based on cell-free and exosomal miRNAs is provided.
[0019] Figure 9 miRNA regulation using hypergeometric distribution test for cancer hallmarks and KEGG pathways is shown. Significantly enriched signaling pathways are shown in the dot plots (P<0.001 for BH regulation).
[0020] Figure 10 A schematic flow chart highlighting the intended use of exosome-based miRNA signatures for screening of PDAC is provided. DETAILED DESCRIPTION
[0021] Unless otherwise defined, the technical and scientific terms used herein have the same meanings as those generally understood by those of ordinary skill in the art. See, for example, Singleton et al., Dictionary of Microbiology and Molecular Biology 2nd Edition, J. Wiley & Sons (New York, NY 1994); Sambrook et al., Molecular Cloning, A Laboratory Manual, Cold Springs Harbor Press (Cold Springs Harbor, NY 1989). Any methods, devices, and materials similar or equivalent to those described herein can be used to practice the present disclosure. The following definitions are provided to facilitate understanding of certain terms frequently used herein and are not intended to limit the scope of the present disclosure.
[0022] As used herein, the term "tumor-derived exosomes" or "exosomes" refers to small (20-300 nm in diameter) vesicles containing a lipid bilayer membrane that enclose an internal space and are produced from cancer cells by direct plasma membrane budding or by fusion of late endosomes with the plasma membrane. Tumor-derived exosomes contain components such as proteins, DNA, mRNA, microRNA, long noncoding RNA, and circular RNA, which play a role in regulating tumor growth, metastasis, and angiogenesis during cancer development.
[0023] "Exosomal RNA" refers to RNA within tumor-derived exosomes or RNA obtained from tumor-derived exosomes. In embodiments, "exosomal RNA" is exosomal miRNA. In embodiments, "exosomal RNA" is exosomal mRNA. Exosomal RNA can be detected and measured by methods known in the art, such as those described herein.
[0024] "Cell-free RNA" or "cf-RNA" refers to RNA that is not within or obtained from tumor-derived exosomes. Cell-free RNA can be detected and measured by methods known in the art, such as those described herein.
[0025] "Cell" refers to a cell that performs metabolic or other functions sufficient to maintain or replicate its genomic DNA. Cells can be identified by methods well known in the art, including, for example, the presence of an intact membrane, staining with a specific dye, the ability to reproduce offspring, or, if gametes are present, the ability to combine with a second gamete to produce viable offspring. Cells can include prokaryotic cells and eukaryotic cells. Prokaryotic cells include, but are not limited to, bacteria. Eukaryotic cells include, but are not limited to, yeast cells and cells derived from plants and animals, such as mammalian (e.g., human) cells. They may be useful when the cells are naturally non-adherent or are treated to be non-adherent to a surface, such as by trypsinization.
[0026] "Nucleic acid" refers to nucleotides (e.g., deoxyribonucleotides or ribonucleotides) and their polymers, or their complements, in single-stranded, double-stranded or multi-stranded forms; or nucleosides (e.g., deoxyribonucleosides or ribonucleosides). In an embodiment, "nucleic acid" does not include nucleosides. The terms "polynucleotide," "oligonucleotide," etc., generally and customarily refer to a linear sequence of nucleotides. The term "nucleoside" generally and customarily refers to a glycosylamine comprising a nucleobase and a pentose (ribose or deoxyribose). Non-limiting examples of nucleosides include cytidine, uridine, adenosine, guanosine, thymidine, and inosine. The term "nucleotide" generally and customarily refers to a single unit of a polynucleotide, i.e., a monomer. Nucleotides can be ribonucleotides, deoxyribonucleotides, or modified forms thereof. Examples of polynucleotides contemplated herein include single-stranded and double-stranded DNA, single-stranded and double-stranded RNA, and hybrid molecules having a mixture of single-stranded and double-stranded DNA and RNA. Examples of nucleic acids (e.g., polynucleotides) encompassed herein include any type of RNA (e.g., mRNA, siRNA, miRNA, and guide RNA) and any type of DNA, genomic DNA, plasmid DNA, and minicircle DNA, and any fragments thereof. In the case of polynucleotides, the term "duplex" refers to a double strand in the usual and customary sense. Nucleic acids can be straight or branched. For example, a nucleic acid can be a linear nucleotide chain or a nucleic acid can be branched, such as whereby the nucleic acid comprises arms or branches of one or more nucleotides. Optionally, branched nucleic acids repeatedly branch to form higher order structures, such as dendrimers, etc.
[0027] A polynucleotide is typically composed of a specific sequence of four nucleotide bases: adenine (A); cytosine (C); guanine (G); and thymine (T) (when the polynucleotide is RNA, uracil (U) represents thymine (T)). Thus, the term "polynucleotide sequence" is an alphabetic representation of a polynucleotide molecule; alternatively, the term can be applied to the polynucleotide molecule itself. This alphabetic representation can be entered into a database in a computer with a central processing unit and used for bioinformatics applications such as functional genomics and homology searches. A polynucleotide may optionally include one or more non-standard nucleotides, nucleotide analogs, and / or modified nucleotides.
[0028] "Conservatively modified variants" apply to both amino acid and nucleic acid sequences. With respect to specific nucleic acid sequences, "conservatively modified variants" refer to those nucleic acids that encode identical or substantially identical amino acid sequences. Due to the degeneracy of the genetic code, many nucleic acid sequences will encode any given protein. For example, the codons GCA, GCC, GCG, and GCU all encode the amino acid alanine. Thus, at each position where alanine is specified by a codon, the codon can be changed to any of the corresponding codons described without changing the encoded polypeptide. Such nucleic acid variations are "silent variations," which are a type of conservatively modified variation. Each nucleic acid sequence encoding a polypeptide herein also describes each possible silent variation of the nucleic acid. Those skilled in the art will recognize that each codon in the nucleic acid (except AUG, which is typically the only codon for methionine, and TGG, which is typically the only codon for tryptophan) can be modified to obtain functionally identical molecules. Therefore, each silent variation of a nucleic acid encoding a polypeptide is implicit in each described sequence.
[0029] As used herein, "microRNA," "microRNA nucleic acid sequence," "miR," "miRNA" refer to nucleic acids that play a role in RNA silencing and post-transcriptional regulation of gene expression. The term includes all forms of miRNA, such as primary, precursor, and mature forms of miRNA. In an embodiment, microRNA (miRNA) is a short (20nt-24nt) non-coding RNA that participates in post-transcriptional regulation of gene expression in multicellular organisms by affecting the stability and translation of mRNA. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs), which can be protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to produce mature miRNA and antisense miRNA star (miRNA*) products. Mature miRNAs are incorporated into the RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational repression or destabilization of the target mRNA.
[0030] Nucleic acids may comprise non-specific sequences. As used herein, the term "non-specific sequence" refers to a nucleic acid sequence containing a series of residues that are not designed to be complementary to any other nucleic acid sequence or that are only partially complementary to any other nucleic acid sequence. For example, a non-specific nucleic acid sequence is a sequence of nucleic acid residues that does not act as an inhibitory nucleic acid when in contact with a cell or organism.
[0031] As used herein, the term "complement" refers to a nucleotide (e.g., RNA or DNA) or a nucleotide sequence that can base pair with a complementary nucleotide or nucleotide sequence. As described herein and as known in the art, the complementary (matching) nucleotide of adenosine is thymidine, and the complementary (matching) nucleotide of guanine is cytosine. Therefore, a complement can include a nucleotide sequence that base pairs with the corresponding complementary nucleotide of a second nucleic acid sequence. The nucleotides of the complement can partially or completely match the nucleotides of the second nucleic acid sequence. When the nucleotides of the complement fully match each nucleotide of the second nucleic acid sequence, the complement forms a base pair with each nucleotide of the second nucleic acid sequence. When the nucleotides of the complement partially match the nucleotides of the second nucleic acid sequence, only some nucleotides of the complement form a base pair with the nucleotides of the second nucleic acid sequence. The example of a complementary sequence includes coding and non-coding sequences, wherein the non-coding sequence contains the complementary nucleotides of the coding sequence, thereby forming the complement of the coding sequence.
[0032] The term "gene" refers to a segment of DNA involved in producing a protein; it includes regions preceding and following the coding region (leader and trailer sequences) as well as intervening sequences (introns) between the individual coding segments (exons). The leader, trailer, and introns contain regulatory elements essential for gene transcription and translation. Furthermore, a "protein gene product" is the protein expressed by a specific gene.
[0033] As used herein, the term "expression" or "expressed" with respect to a gene refers to the transcription and / or translation product of the gene. The expression level of a DNA molecule in a cell can be determined based on the amount of the corresponding RNA present in the cell or the amount of protein encoded by the DNA produced by the cell. The expression level of a non-coding nucleic acid molecule (e.g., miRNA, mRNA) can be detected by standard PCR or Northern blotting methods well known in the art. See Sambrook et al., 1989 Molecular Cloning: A Laboratory Manual, 18.1-18.88.
[0034] The term "expression level", "amount" or "level" of a biomarker is a detectable level in a biological sample. "Expression" generally refers to the process by which information (e.g., genetically encoded and / or epigenetic) is converted into a structure that exists and operates in a cell. Thus, "expression" can refer to transcription into polynucleotides, translation into polypeptides, or even polynucleotide and / or polypeptide modifications (e.g., post-translational modifications of polypeptides). Fragments of transcribed polynucleotides, translated polypeptides, or polynucleotide and / or polypeptide modifications (e.g., post-translational modifications of polypeptides) should also be considered to be expressed, regardless of whether they are derived from transcripts produced by alternative splicing or degraded transcripts, or from post-translational processing of polypeptides, such as by proteolysis. "Expressed genes" include those that are transcribed into polynucleotides as mRNA and subsequently translated into polypeptides, and also include those that are transcribed into RNA but not translated into polypeptides (e.g., miRNA, transfer RNA, ribosomal RNA, non-coding RNA). Expression levels can be measured by methods known to those skilled in the art and also disclosed herein. The expression level or amount of a biomarker (e.g., RNA, miRNA) can be used to diagnose and / or treat subjects with pancreatic cancer.
[0035] The term "elevated expression level" or "elevated level" of gene expression is a gene expression level that is higher than the gene expression level in the control. The control can be any suitable control as described herein. In embodiments, the "elevated expression level" of a biomarker gene compared to a control (when the expression level of the biomarker is greater than the corresponding control) is, for example, relative to the control, an expression level that is increased by about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98% or 99% or greater. In embodiments, the "elevated expression level" of a biomarker gene is an amount that is statistically significantly greater than the expression level of the control.
[0036] The term "does not have an elevated expression level" or "not elevated" expression level is a gene expression level that is approximately the same as (or lower than) the gene expression level in the control. The control can be any suitable control as described herein. In embodiments, "approximately the same as" is + / - 25% of the expression level of the biomarker gene in the control. In embodiments, "approximately the same as" is + / - 20% of the expression level of the biomarker gene in the control. In embodiments, "approximately the same as" is + / - 15% of the expression level of the biomarker gene in the control. In embodiments, "approximately the same as" is + / - 10% of the expression level of the biomarker gene in the control. In embodiments, "approximately the same as" is + / - 5% of the expression level of the biomarker gene in the control. In embodiments, the "not elevated" or "not elevated" expression level of a biomarker gene is an amount that is statistically significantly different from the expression level of the control.
[0037] The terms "biomarker gene" and "biomarker" are used interchangeably and according to their ordinary and common meanings. In embodiments, a biomarker is a gene or a group of genes (i.e., biomarker genes). Biomarkers include, but are not limited to, polynucleotides (e.g., DNA and / or RNA), polynucleotide copy number changes (e.g., DNA copy number), polypeptides, or polypeptide and polynucleotide modifications (e.g., post-translational modifications). In embodiments, a biomarker refers to an RNA (e.g., miRNA) whose expression level is associated with a specific biological state, particularly a state associated with pancreatic cancer.
[0038] Biomarker levels can be detected at the protein or gene expression level. Proteins expressed by biomarkers can be quantified by immunohistochemistry (IHC) or flow cytometry using antibodies that detect proteins. Biomarker expression can be quantified by multiple platforms, such as real-time polymerase chain reaction (rtPCR), Nanostring, RNAseq, or in situ hybridization. As measured by Nanostring, there is a range of biomarker expressions. In embodiments, quantitative rtPCR, Nanostring, RNAseq, and in situ hybridization are platforms for quantitative biomarker gene expression. For Nanostring, RNA is extracted from a biological sample, and a known amount of RNA is placed on a Nanostring machine and gene expression detection is performed using gene-specific probes. The number of biomarker counts within the sample is determined and normalized to a set of housekeeping genes. To determine the threshold value of increased or decreased biomarker levels, one skilled in the art can assess the biomarker levels of the control group samples and select the 10th percentile, 20th percentile, 25th percentile, 30th percentile, 40th percentile, 50th percentile, 60th percentile, 70th percentile, 75th percentile, 80th percentile or 90th percentile of biomarker gene expression. In an embodiment, increased or decreased biomarker expression can be determined by calculating the H score of biomarker expression. Thus, increased or decreased biomarker expression can have an H score. As used herein, an "H score" or "Histoscore" is a numerical value determined by a semi-quantitative method commonly known for immunohistochemical assessment of protein expression in tumor samples. The H score can be calculated using the following formula: [1×(% cell 1+)+2×(% cell 2+)+3×(% cell 3+)]. According to this formula, the H score is calculated by determining the percentage of cells with a given staining intensity level (i.e., from lowest to highest intensity level: 1+, 2+, or 3+), weighting the percentage of cells with a given intensity level by multiplying the percentage of cells by a factor (e.g., 1, 2, or 3) that gives a greater relative weight to cells with higher intensity membrane staining, and summing the results to obtain the H score. Typically, the H score ranges from 0 to 300. Further description of the determination of the H score in tumor cells can be found in Hirsch et al., J Clin Oncol 21:3798-3807, 2003 and John et al., Oncogene 28:S14-S23, 2009. IHC or other methods known in the art can be used to detect biomarker expression.
[0039] "Control" or "controlled experiment" is used in its ordinary conventional sense to refer to an assay, comparison, or experiment in which the experimental subjects or reagents are treated as in parallel experiments, except that the experimental procedures, reagents, or variables are omitted. In embodiments, the control is used as a standard of comparison when evaluating the effects of the experiment. In embodiments, the control is a measurement of RNA activity or level. In embodiments, the control is a healthy patient or a population of healthy patients. In embodiments, the control is an average value from a population of similar patients, for example, healthy patients with similar medical backgrounds, ages, weights, etc. In embodiments, the control is a healthy patient or a population of healthy patients. In embodiments, healthy patients may be referred to as non-diseased patients or non-diseased controls. In embodiments, the control is a population of non-diseased patients. In embodiments, non-diseased patients are patients who do not have cancer. In embodiments, non-diseased patients are patients who do not have pancreatic cancer. In embodiments, the control is a patient who does not have cancer or a population of patients who do not have cancer. In embodiments, the control is a patient who does not have pancreatic cancer or a population of patients who do not have pancreatic cancer. In embodiments, the control is a patient who does not have PDAC or a population of patients who do not have PDAC. In embodiments, the control is an average value from a population of healthy patients. The control can also be obtained from the same patient, for example, from a sample obtained earlier before becoming ill or before treatment. Those skilled in the art will recognize that the control can be designed to evaluate any number of parameters. In embodiments, the control is a negative control. In embodiments, as in some embodiments related to the expression level of a subset of genes / proteins or genes / proteins, the control includes the average amount of expression (for example, protein or mRNA) in a subject (for example, suffering from cancer) colony or a healthy or common colony. In embodiments, the control includes the average amount (for example, expression) in a colony, wherein the number (n) of the subject is 5 or more, 20 or more, 50 or more, 100 or more, 1,000 or more, etc. In embodiments, the control is a standard control. In embodiments, the standard control is the expression level of a biomarker (for example, RNA, miRNA) associated with the diagnosis of pancreatic cancer in a subject. In embodiments, the standard control is the expression level of a biomarker (for example, RNA, miRNA) associated with a healthy subject (i.e., a subject not suffering from pancreatic cancer). Those skilled in the art will understand that which controls are valuable in a given situation and can analyze data based on a comparison with a control value. Controls are also valuable for determining the significance of data. For example, if the values of a given parameter vary widely in the controls, the variation in the test samples will not be considered significant.
[0040] The term "healthy patient" refers to a non-diseased patient. In embodiments, a healthy patient is a patient without cancer. In embodiments, a healthy patient is a patient who does not suffer from pancreatic cancer (e.g., PDAC).
[0041] The term "recombinant" when used with respect to, for example, a cell, or a nucleic acid, protein, or vector, means that the cell, nucleic acid, protein, or vector has been modified by the introduction of a heterologous nucleic acid or protein or by the alteration of a native nucleic acid or protein, or that the cell is derived from a cell so modified. Thus, for example, a recombinant cell expresses genes that are not present in the native (non-recombinant) form of the cell or expresses native genes that are otherwise abnormally expressed, underexpressed, or not expressed at all. Transgenic cells and plants are those that express heterologous genes or coding sequences, typically as a result of recombinant methods.
[0042] The term "heterologous," when used with reference to a portion of a nucleic acid, means that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature. For example, nucleic acids are often recombinantly produced, having two or more sequences from unrelated genes arranged to produce a new functional nucleic acid, such as a promoter from one source and a coding region from another source. Similarly, a heterologous protein means that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).
[0043] When referring to a protein or peptide, the phrase "specifically (or selectively) binds to" or "specifically (or selectively) immunoreacts with" an antibody means that the presence of the protein is determined, typically in a heterogeneous population of proteins and other biological agents. Thus, under specified immunoassay conditions, the binding of a specified antibody to a particular protein is at least twice the background, and more typically more than 10 to 100 times the background. Specific binding to an antibody under such conditions requires selection of antibodies that are specific for a particular protein. For example, polyclonal antibodies can be selected to obtain only a subset of antibodies that specifically immunoreact with a selected antigen and not with other proteins. This selection can be achieved by subtracting antibodies that cross-react with other molecules. A variety of immunoassay formats can be used to select antibodies that specifically immunoreact with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select antibodies that specifically immunoreact with a protein (for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity, see, for example, Harlow and Lane, Using Antibodies, A Laboratory Manual (1998)).
[0044] When applied to nucleic acids, viruses or proteins, the terms "isolated" or "isolated" mean that the nucleic acid, virus or protein is substantially free of other cellular components with which it is associated in its native state. It can, for example, be in a homogeneous state and can be in a dry state or in aqueous solution. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. RNA, which is the predominant species present in the preparation, is substantially purified.
[0045] The "percentage of sequence identity" is determined by comparing two optimally aligned sequences in a comparison window, wherein for optimal alignment of the two sequences, the portion of the polynucleotide or polypeptide sequence in the comparison window may include additions or deletions (i.e., gaps) compared to the reference sequence (which does not include additions or deletions). The percentage is calculated by determining the number of positions where the identical nucleic acid base or amino acid residue occurs in the two sequences to obtain the number of matched positions, dividing the number of matched positions by the total number of positions in the comparison window, and multiplying the result by 100 to obtain the percentage of sequence identity.
[0046] In the context of two or more nucleic acid or polypeptide sequences, the term "identical" or "identity" percentage refers to two or more sequences of identical or specified percentages of amino acid residues or identical nucleotides (i.e., about 60% identity over a specified region, preferably 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identity when compared and aligned for maximum correspondence over a comparison window or specified region) (e.g., www.ncbi.nlm.nih.gov / BLAST / / , etc.). Such sequences are then referred to as "substantially identical." This definition also refers to or may be applied to the complementary sequence of a test sequence. This definition also includes sequences with deletions and / or additions, as well as sequences with substitutions. As described below, preferred algorithms can account for gaps, etc. Preferably, identity exists over a region that is at least about 25 amino acids or nucleotides in length, or more preferably over a region that is 50-100 amino acids or nucleotides in length.
[0047] The "position" of an amino acid or nucleotide base is represented by a number that sequentially identifies each amino acid (or nucleotide base) in the reference sequence based on its position relative to the N-terminus (or 5' end). Since deletions, insertions, truncations, fusions, etc. must be considered when determining the optimal alignment, the numbering of amino acid residues in a test sequence, as determined by counting only from the N-terminus, is not necessarily the same as the numbering of their corresponding positions in the reference sequence. For example, where a variant has a deletion relative to the aligned reference sequence, there will be no amino acid in the variant corresponding to the position at the deletion site in the reference sequence. In the case of an insertion in the aligned reference sequence, the insertion will not correspond to the numbered amino acid position in the reference sequence. In the case of truncations or fusions, there may be stretches of amino acids in the reference sequence or aligned sequence that do not correspond to any amino acid in the corresponding sequence.
[0048] When used in the context of the numbering of a given amino acid or polynucleotide sequence, the term "reference number" or "corresponding to" refers to the numbering of the residues of a given reference sequence when comparing the given amino acid or polynucleotide sequence to the reference sequence.
[0049] As used herein, the term "about" means a range of values that encompasses the specified value and that one of ordinary skill in the art would consider reasonably similar to the specified value. In embodiments, "about" means within a standard deviation using measurements generally accepted in the art. In embodiments, "about" means a range extends to + / - 10% of the specified value. In embodiments, "about" includes the specified value.
[0050] The singular terms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.
[0051] As used herein, "therapeutic agent" or "anti-cancer agent" refers to an agent (e.g., a compound, a pharmaceutical composition) that will have the intended therapeutic effect when administered to a subject, for example, treating or ameliorating pancreatic cancer or its symptoms, including any objective or subjective therapeutic parameter, such as reduction; remission; alleviation of symptoms or making the patient more tolerant to the cancer; slowing the rate of regression or decline; making the final point of regression less debilitating; or improving the patient's physical or mental health.
[0052] "Biological sample" or "sample" refers to the material obtained from or derived from a subject or patient. Biological samples include tissue sections, such as biopsy and autopsy samples, and frozen sections for histological purposes. Such samples include body fluids, such as blood and blood fractions or products (such as serum, plasma, platelets, red blood cells, etc.), sputum, tissue, cultured cells (such as primary culture, explants and transformed cells) feces, urine, synovial fluid, joint tissue, synovial tissue, synoviocytes, fibroblast-like synoviocytes, macrophage-like synoviocytes, immune cells, hematopoietic cells, fibroblasts, macrophages, T cells, etc. In embodiments, the biological sample is blood. In embodiments, the biological sample is a serum sample (for example, the fluid and solute components of blood without coagulation factors). In embodiments, the biological sample is a plasma sample (for example, the liquid portion of blood). In embodiments, the biological sample is the cell-free RNA obtained from blood. In embodiments, the biological sample is an exosome obtained from a blood sample, wherein the exosome comprises RNA. In embodiments, the biological sample is exosomes obtained from a serum sample, wherein the exosomes comprise RNA. In embodiments, the biological sample is exosomes obtained from a plasma sample, wherein the exosomes comprise RNA.
[0053] "Liquid biological sample" refers to a liquid material obtained or derived from a subject or patient. Liquid biological samples include body fluids such as blood and blood fractions or products (e.g., serum, plasma, platelets, red blood cells, etc.), sputum, urine, synovial fluid, etc. In embodiments, the liquid sample is a blood sample.
[0054] The term "diagnosis" is used according to its plain and ordinary meaning and refers to the identification or likelihood of the presence of a disease (eg, pancreatic cancer) or outcome in a subject.
[0055] "Image-based screening" refers to a method of using imaging technology to detect cancer or tumors in a patient. Exemplary types of image-based screening include X-rays, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and ultrasound. In embodiments of the methods described herein, the image-based screening is CT, MRI, or ultrasound. In embodiments, the ultrasound is endoscopic ultrasonography (EUS). In embodiments of the methods described herein, the image-based screening is CT, MRI, or EUS. In embodiments of the methods described herein, the image-based screening is MRI or EUS. In embodiments of the methods described herein, the image-based screening is CT. In embodiments of the methods described herein, the image-based screening is MRI. In embodiments of the methods described herein, the image-based screening is EUS.
[0056] The term "treatment" is used according to its ordinary and common meaning and broadly includes any method for obtaining a beneficial or desired result (including a clinical result) in the subject's condition. Beneficial or desired clinical results may include, but are not limited to: alleviating or improving one or more symptoms or conditions, alleviating the extent of the disease, stabilizing (i.e., not worsening) the disease state, delaying or slowing the progression of the disease, improving or alleviating the disease state, and alleviating, whether local or total, and whether detectable or undetectable. Treatment can inhibit the spread of the disease; alleviate the symptoms of the disease; remove the underlying cause of the disease in whole or in part; shorten the duration of the disease; or perform a combination of these things. Methods of treatment include administering a therapeutically effective amount of an active agent to the subject. The term "treatment" does not include prevention.
[0057] The term "prevent" is used according to its plain and ordinary meaning and refers to reducing the occurrence of symptoms of a disease in a patient or preventing the occurrence of the disease. Prevention can be complete (no detectable symptoms) or partial, whereby fewer symptoms are observed than would occur in the absence of treatment.
[0058] "Effective amount" is an amount sufficient to achieve the purpose (e.g., to achieve the effect of administration, to treat a disease). An example of an "effective amount" is an amount sufficient to help treat, prevent or alleviate one or more symptoms of a disease, which may also be referred to as a "therapeutically effective amount." "Reduction" of one or more symptoms (and grammatical equivalents of this phrase) means reducing the severity or frequency of one or more symptoms, or eliminating one or more symptoms. The exact amount will depend on the purpose of treatment and will be determined by those skilled in the art using known techniques. In an embodiment, a "therapeutically effective amount" refers to the amount of a therapeutic agent sufficient to treat or improve pancreatic cancer as described above. For any compound described herein, a therapeutically effective amount may initially be determined based on a cell culture assay. As measured using methods described herein or known in the art, the target concentration will be those concentrations of one or more active compounds that can achieve the methods described herein. As is well known in the art, a therapeutically effective amount for humans may also be determined based on an animal model. For example, a human dose may be formulated to achieve a concentration found to be effective for animals. As described above, the dose in the human body may be adjusted by monitoring the effectiveness of the compound and by adjusting the dose upward or downward. Adjusting the dosage based on the above methods and other methods to achieve maximum efficacy in humans is entirely within the capabilities of ordinary technicians. The dosage can vary depending on the patient's needs and the therapeutic agent being used. The dosage administered to the patient should be sufficient to elicit a beneficial therapeutic response in the patient over time. The size of the dosage will also be determined by the presence, nature, and extent of any adverse side effects. Determining the appropriate dosage for a specific situation is within the skill of the practitioner. Typically, treatment is initiated with a smaller dose than the optimal dose of the compound. Thereafter, the dosage is increased in small increments until the optimal effect is achieved in a number of cases. The dosage and interval can be individually adjusted to provide a level of the compound administered that is effective for the specific clinical indication being treated. This will provide a treatment regimen commensurate with the severity of the patient's disease state. "Therapeutically effective amount" can also be found on the label or prescribing information of commercially available therapeutic agents.
[0059] As used herein, the term "administering" means oral administration, administration in the form of a suppository, topical contact, intravenous, parenteral, intraperitoneal, intramuscular, intralesional, intrathecal, intranasal or subcutaneous administration to a subject, or implantation of a slow-release device (e.g., a mini-osmotic pump). Administered by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal or transdermal). Parenteral administration includes, for example, intravenous, intramuscular, intraarterial, intradermal, subcutaneous, intraperitoneal, intraventricular and intracranial. Other modes of delivery include, but are not limited to, the use of liposome formulations, intravenous infusion, transdermal patches, etc. In an embodiment, administering does not include administering any active agent other than the stated active agent.
[0060] The term "patient" or "subject" is used according to its ordinary and common meaning and refers to a living organism that is suffering from or susceptible to a disease that can be treated by administering a pharmaceutical composition (such as an anticancer agent and a therapeutic agent). Non-limiting examples include humans, other mammals, cattle, rats, mice, dogs, cats, monkeys, and other non-mammals. In embodiments, the patient is a human. In embodiments, the human patient is at least 45 years old. In embodiments, the human patient is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the human patient is at least 45 years old and has new-onset diabetes. In embodiments, the human patient is at least 50 years old and has new-onset diabetes. In embodiments, the human patient is at least 55 years old and has new-onset diabetes. In embodiments, the human patient has a family history of pancreatic cancer. In embodiments, the human patient suffers from obesity. In embodiments, the human patient has a history of pancreatitis. In embodiments, the human patient has a history of chronic pancreatitis.
[0061] The terms "metastasis," "metastatic," and "metastatic cancer" are used interchangeably and refer to the spread of a proliferative disease or condition (e.g., cancer) from one organ to another non-adjacent organ or body part. Cancer occurs at a site of origin (e.g., the pancreas), which is referred to as a primary tumor, such as primary pancreatic cancer. Some cancer cells in the primary tumor or site of origin acquire the ability to penetrate and infiltrate normal tissues surrounding the local area, and / or penetrate the lymphatic system or the walls of the vascular system through systemic circulation to other sites and tissues in the body. A second clinically detectable tumor formed by the cancer cells of the primary tumor is referred to as a metastatic or secondary tumor. When cancer cells metastasize, it is speculated that the metastatic tumor and its cells are similar to the primary tumor. Therefore, if pancreatic cancer metastasizes to the lymph nodes, the secondary tumors at the lymph node site are composed of pancreatic cancer cells rather than abnormal lymph node cells. Secondary tumors in the lymph nodes are referred to as lymph node metastases. Therefore, the phrase metastatic cancer refers to a disease in which a subject has or has had a primary tumor and has one or more secondary tumors. The phrase non-metastatic cancer or a subject having non-metastatic cancer refers to a disease in which the subject has a primary tumor but does not have one or more secondary tumors.
[0062] "PDAC" refers to pancreatic ductal adenocarcinoma, a type of pancreatic cancer. PDAC accounts for over 90% of pancreatic cancer cases. Symptoms of pancreatic cancer include diabetes, high blood sugar, jaundice, sudden weight loss, abdominal pain, back pain, persistent loss of appetite, light-colored stools, bloating, nausea, vomiting, or diarrhea. In one embodiment, the symptom of pancreatic cancer is new-onset diabetes. In one embodiment, the symptom of pancreatic cancer is new-onset high blood sugar. In one embodiment, the symptom of pancreatic cancer is diabetes. In one embodiment, the symptom of pancreatic cancer is high blood sugar. In one embodiment, the diabetes is new-onset diabetes or pre-existing diabetes.
[0063] The staging of pancreatic cancer is well known in the art.For example, "1st phase" pancreatic cancer refers to the pancreatic cancer found only in the pancreas.1st phase includes IA phase and IB phase, wherein IA phase is defined as T1, N0, M0, and IB phase is defined as T2, N0, M0). "2nd phase" pancreatic cancer refers to that pancreatic cancer may have metastasized to adjacent tissues and organs or lymph nodes near the pancreas.2nd phase pancreatic cancer includes IIA phase and IIB phase, wherein IIA phase is defined as T3, N0, M0, and IIB phase is defined as T1 / T2 / T3, N1, M0. "3rd phase" pancreatic cancer refers to the pancreatic cancer (T4, any N, M0) that has spread to the main blood vessels near the pancreas and may have spread to adjacent lymph nodes but has not spread to distant sites. "4th phase" pancreatic cancer refers to the pancreatic cancer (any T, any N, M1) that can be any size and has spread to distant organs (for example, liver, lung, peritoneal cavity) and may have spread to lymph nodes or organs near the pancreas and tissue. The term "T1" means that the tumor is only in the pancreas and is 2 cm or smaller in size. The term "T2" means that the tumor is only in the pancreas and is larger than 2 cm and smaller than 4 cm. The term "T3" means that the tumor is larger than 4 cm and extends beyond the pancreas but does not involve the aorta or vein near the pancreas. The term "T4" means that the tumor extends beyond the pancreas into the aorta or vein near the pancreas. The term "N0" means that cancer is not found in the local lymph nodes. The term "N1" means that the cancer has spread to 1 to 3 local lymph nodes. The term "N2" means that the cancer has spread to 4 or more local lymph nodes. The term "M0" means that the cancer has not spread to other parts of the body. The term "M1" means that the cancer has spread to another part of the body, including distant lymph nodes.
[0064] The term "carbohydrate antigen 19-9" or "CA19-9" refers to serum CA19-9, which is the most well-documented and widely used serum biomarker in patients with PDAC (references 2, 3, 12). Although CA19-9 is commonly used to monitor disease progression and treatment response in pancreatic cancer, it lacks satisfactory sensitivity or specificity for screening and early detection of patients with PDAC. (references 13 to 14). 15%-25% of patients with PDAC, including those in the early stages (e.g., stages 1 and 2), often exhibit CA19-9 levels of less than 37 U / ml, which is considered normal. (references 15 to 16). In addition, 5%-10% of the general population is Lewis antigen negative, with no or low CA19-9 secretion (reference 17). The phrase "normal CA19-9 levels" refers to CA19-9 levels of less than 37 U / ml. The phrase "elevated CA19-9 levels" refers to CA19-9 levels of 37 U / ml or higher. The phrase "elevated carbohydrate antigen 19-9 level" refers to an elevated CA19-9 level obtained in a patient when compared to a CA19-9 level obtained at an earlier time point. An "elevated carbohydrate antigen 19-9 level" can be greater than or less than 37 U / ml at any time point.
[0065] Treatment
[0066] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, comprising administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, administering to the patient an image-based screening, surgically removing all or part of the pancreas from the patient, or a combination of two or more thereof; wherein a biological sample obtained from the patient comprises elevated expression levels of an RNA relative to a control; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p , cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, or a combination of two or more thereof. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least five RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least six RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least seven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least eight RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least nine RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least ten RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least eleven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least twelve RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA includes cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes two RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes five RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes six RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes seven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes eight RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes nine RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes ten RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes eleven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes twelve RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient has diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient has new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is 1 phase pancreatic cancer or 2 phase pancreatic cancer. In embodiments, the pancreatic cancer is 1 phase pancreatic cancer. In embodiments, the pancreatic cancer is IA phase. In embodiments, the pancreatic cancer is IIB phase. In embodiments, the pancreatic cancer is 2 phase pancreatic cancer. In embodiments, the pancreatic cancer is IIA phase. In embodiments, the pancreatic cancer is IIB phase. In embodiments, pancreatic cancer is stage 3 pancreatic cancer or stage 4 pancreatic cancer. In embodiments, pancreatic cancer is stage 3 pancreatic cancer. In embodiments, pancreatic cancer is stage 4 pancreatic cancer. In embodiments, pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer or stage 3 pancreatic cancer. In embodiments, pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, stage 3 pancreatic cancer or stage 4 pancreatic cancer. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient.In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent and administering to the patient an effective amount of radiation therapy. In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent and surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method comprises administering to the patient an effective amount of radiation therapy. In embodiments, the method comprises surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering to the patient an image-based screening, administering to the patient an effective amount of an anticancer agent, and administering to the patient an effective amount of radiation therapy. In embodiments, the method comprises administering to the patient an image-based screening, and administering to the patient an effective amount of an anticancer agent. In embodiments, the method comprises administering to the patient an image-based screening. In an embodiment, the biological sample obtained from the patient further comprises an elevated expression level of an RNA relative to a control, the RNA being selected from the group consisting of: cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free let-7f-5p, cell-free miR-3 exosomal miR-69-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-375-3p, exosomal miR-199a-5p, and combinations of two or more thereof. In an embodiment, the biological sample obtained from the patient further comprises elevated expression levels of a RNA relative to a control, the RNA being selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, and a combination of two or more thereof.In an embodiment, the biological sample obtained from the patient further comprises elevated expression levels of an RNA relative to a control, the RNA being selected from the group consisting of cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, and a combination of two or more thereof.
[0067] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the methods comprising administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the pancreas of the patient, or a combination of two or more thereof; wherein a biological sample obtained from the patient comprises elevated expression levels of RNA relative to a control; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, or a combination of two or more thereof. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises at least three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises at least four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises two RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises three RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises four RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p.In embodiments, RNA includes cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p and cell-free miR-23b-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient suffers from new-onset diabetes. In embodiments, the patient suffers from diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient suffers from new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has an increased carbohydrate antigen 19-9 level, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, e-cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer or stage 2 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer. In embodiments, the pancreatic cancer is stage IA. In embodiments, the pancreatic cancer is stage IB. In embodiments, the pancreatic cancer is stage 2 pancreatic cancer. In embodiments, the pancreatic cancer is stage IIA. In embodiments, the pancreatic cancer is stage IIB. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer or stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, or stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, stage 3 pancreatic cancer, or stage 4 pancreatic cancer. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population. In embodiments, the method includes administering an effective amount of an anticancer agent to the patient. In embodiments, the method includes administering an effective amount of an anticancer agent to the patient and administering an effective amount of radiation therapy to the patient. In embodiments, the method includes administering an effective amount of an anticancer agent to the patient and surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method includes administering an effective amount of radiation therapy to the patient. In embodiments, the method includes surgically removing all or part of the patient's pancreas.In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering to the patient an image-based screening, administering to the patient an effective amount of an anticancer agent, and administering to the patient an effective amount of radiation therapy. In embodiments, the method comprises administering to the patient an image-based screening, and administering to the patient an effective amount of an anticancer agent. In embodiments, the method comprises administering to the patient an image-based screening. In embodiments, the biological sample obtained from the patient further comprises an expression level of an RNA that is elevated relative to a control, the RNA being selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, and a combination of two or more thereof. In embodiments, the biological sample obtained from the patient further comprises an elevated expression level of an RNA selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, and a combination of two or more thereof, relative to a control. In embodiments, the biological sample obtained from the patient further comprises an elevated expression level of an RNA selected from the group consisting of cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, and a combination of two or more thereof, relative to a control.
[0068] Provided herein are methods of treating pancreatic cancer in a patient in need thereof, the method comprising administering to the patient an effective amount of an anti-cancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the patient's pancreas, or a combination of two or more thereof; wherein a biological sample obtained from the patient comprises elevated expression levels of an RNA relative to a control; wherein the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, or a combination of two or more thereof. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least three RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least four RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least five RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least six RNAs selected from the group consisting of exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least seven RNAs selected from the group consisting of exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises two RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises three RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises four RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises five RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes six RNAs selected from the group consisting of exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises seven RNAs selected from the group consisting of exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient suffers from diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient suffers from new-onset diabetes and is at least 50 years old. In embodiments, human patients are at least 55 years old. In embodiments, human patients are at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more of them. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, pancreatic cancer is phase 1 pancreatic cancer. In embodiments, pancreatic cancer is phase IA. In embodiments, pancreatic cancer is phase IB. In embodiments, the pancreatic cancer is stage 2 pancreatic cancer. In embodiments, the pancreatic cancer is stage IIA. In embodiments, the pancreatic cancer is stage IIB. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer or stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, or stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, stage 3 pancreatic cancer, or stage 4 pancreatic cancer. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample.In embodiments, the control is the average expression level of RNA in a healthy patient population. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient and administering an effective amount of radiotherapy to the patient. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient and surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method comprises administering an effective amount of radiotherapy to the patient. In embodiments, the method comprises surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiotherapy to the patient and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiotherapy to the patient and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an image-based screening to the patient, administering an effective amount of an anticancer agent to the patient and administering an effective amount of radiotherapy to the patient. In embodiments, the method comprises administering an image-based screening to the patient and administering an effective amount of an anticancer agent to the patient. In embodiments, the method comprises administering an image-based screening to the patient. In an embodiment, the biological sample obtained from the patient further comprises an elevated expression level of a RNA relative to a control, the RNA being selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-375-3p, exosomal miR-199a-5p, and a combination of two or more thereof. In embodiments, the biological sample obtained from the patient further comprises an elevated expression level of an RNA relative to a control, the RNA being selected from the group consisting of: exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, and a combination of two or more thereof. In embodiments, the biological sample obtained from the patient further comprises an elevated expression level of an RNA relative to a control, the RNA being selected from the group consisting of: exosomal miR-375-3p, exosomal miR-199a-5p, and a combination of two or more thereof.
[0069] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the methods comprising administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the pancreas from the patient, or a combination of two or more thereof; wherein a biological sample obtained from the patient comprises elevated expression levels of an RNA relative to a control; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p , exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosome miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof. In embodiments, elevated RNA expression levels indicate that the patient has pancreatic cancer. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer or stage 2 pancreatic cancer. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In an embodiment, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, or a combination of two or more thereof.In embodiments, the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof. In embodiments, the control is the average expression level of the RNA in a population of healthy patients.
[0070] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the methods comprising administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the pancreas of the patient, or a combination of two or more thereof; wherein a biological sample obtained from the patient comprises elevated expression levels of RNA relative to a control; the RNA comprising cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, or a combination of two or more thereof. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least three RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least four RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least five RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least six RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least seven RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least eight RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least nine RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises at least ten RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least eleven RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a- 5p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least twelve RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a- 5p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least thirteen RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a- 5p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free miR -30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises two RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises three RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises four RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises five RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises six RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises seven RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises eight RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises nine RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises ten RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises eleven RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises twelve RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises thirteen RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA includes cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free miR In some embodiments, the patient has symptoms of pancreatic cancer. In some embodiments, the patient has new-onset diabetes. In some embodiments, the patient has diabetes. In some embodiments, the patient is at least 45 years old. In some embodiments, the patient has new-onset diabetes and is at least 50 years old. In some embodiments, the human patient is at least 55 years old. In some embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has elevated carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, e-cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer. In embodiments, the pancreatic cancer is phase IA. In embodiments, the pancreatic cancer is phase IB. In embodiments, the pancreatic cancer is phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase IIA. In embodiments, the pancreatic cancer is phase IIB. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population.In embodiments, the method comprises administering to the patient an effective amount of an anti-cancer agent, surgically removing all or part of the patient's pancreas, or a combination thereof.
[0071] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the method comprising administering to the patient an effective amount of an anti-cancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the patient's pancreas, or a combination of two or more thereof; wherein a biological sample obtained from the patient comprises elevated expression levels of RNA relative to a control; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, or a combination of two or more thereof. In an embodiment, the RNA includes at least two RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes at least three RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes at least four RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes at least five RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p.In embodiments, the RNA includes cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes two RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes three RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p and cell-free miR-23b-3p. In an embodiment, the RNA includes four RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p and cell-free miR-23b-3p. In an embodiment, the RNA includes five RNAs selected from the group consisting of: cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p and cell-free miR-23b-3p. In embodiments, the RNA comprises cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient has diabetes.In embodiments, the patient is at least 45 years old. In embodiments, the patient suffers from new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer. In embodiments, the pancreatic cancer is phase 2 pancreatic cancer. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient, surgically removing all or part of the patient's pancreas, or a combination thereof. In embodiments, the control is the average expression level of the RNA in a population of healthy patients.
[0072] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the methods comprising administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the pancreas from the patient, or a combination of two or more thereof; wherein a biological sample obtained from the patient comprises elevated expression levels of RNA relative to a control; wherein the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR- exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, or a combination of two or more thereof. In embodiments, the RNA includes at least two RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least three RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA includes at least four RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least five RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least six RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least seven RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA includes at least seven RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes two RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes three RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes four RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes five RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes six RNAs selected from the group consisting of exosome miR-1260a, exosome miR-141-3p, exosome miR-143-3p, exosome miR-148a-3p, exosome miR-200c-3p, exosome miR-216a-5p, exosome miR-34a-5p, exosome miR-1260b, exosome miR-145-5p, exosome miR-200a-3p, exosome miR-200b-3p, exosome miR-216b-5p, exosome miR-217-5p, exosome miR-429, and exosome miR-145-3p. In an embodiment, the RNA includes seven RNAs selected from the group consisting of exosome miR-1260a, exosome miR-141-3p, exosome miR-143-3p, exosome miR-148a-3p, exosome miR-200c-3p, exosome miR-216a-5p, exosome miR-34a-5p, exosome miR-1260b, exosome miR-145-5p, exosome miR-200a-3p, exosome miR-200b-3p, exosome miR-216b-5p, exosome miR-217-5p, exosome miR-429, and exosome miR-145-3p.In an embodiment, the RNA includes seven RNAs selected from the group consisting of exosome miR-1260a, exosome miR-141-3p, exosome miR-143-3p, exosome miR-148a-3p, exosome miR-200c-3p, exosome miR-216a-5p, exosome miR-34a-5p, exosome miR-1260b, exosome miR-145-5p, exosome miR-200a-3p, exosome miR-200b-3p, exosome miR-216b-5p, exosome miR-217-5p, exosome miR-429, and exosome miR-145-3p. In embodiments, the RNA comprises exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient has diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient suffers from new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer. In embodiments, the pancreatic cancer is phase IA. In embodiments, the pancreatic cancer is phase IB. In embodiments, the pancreatic cancer is phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase IIA. In embodiments, the pancreatic cancer is stage IIB. In embodiments, the biological sample obtained from the patient has normal CA19-9 levels. In embodiments, the biological sample obtained from the patient has elevated CA19-9 levels. In embodiments, the biological sample obtained from the patient is Lewis antigen negative.In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a population of healthy patients. In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent, surgically removing all or part of the patient's pancreas, or a combination thereof.
[0073] Methods of detection and treatment
[0074] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the methods comprising: (i) detecting elevated expression levels of RNA in a biological sample obtained from the patient relative to a control, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-14 The invention provides a method for treating pancreatic cancer by administering an effective amount of an anticancer agent to the patient, an effective amount of radiotherapy to the patient, surgical resection of all or part of the pancreas of the patient, or a combination of two or more thereof. The method further provides a method for treating pancreatic cancer by administering an effective amount of an anticancer agent to the patient, an effective amount of radiotherapy to the patient, surgical resection of all or part of the pancreas of the patient, or a combination of two or more thereof. The method further provides a method for treating pancreatic cancer by administering an effective amount of an anticancer agent to the patient, an effective amount of radiotherapy to the patient, surgical resection of all or part of the pancreas of the patient, or a combination of two or more thereof. The method further provides a method for treating pancreatic cancer by administering an effective amount of an anticancer agent to the patient, an effective amount of radiotherapy to the patient, surgical resection of all or part of the pancreas of the patient, or a combination of two or more thereof. In an embodiment, the method comprises administering an image-based screening to the patient, administering an effective amount of an anticancer agent to the patient, and administering an effective amount of radiotherapy to the patient. In embodiments, the method comprises administering an image-based screen to the patient and administering an effective amount of an anticancer agent to the patient. In embodiments, the method comprises administering an image-based screen to the patient. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least five RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least six RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least seven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least eight RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least nine RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least ten RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least eleven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least twelve RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes two RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes five RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes six RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes seven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes eight RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes nine RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes ten RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes eleven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes twelve RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient has diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient has new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is 1 phase pancreatic cancer or 2 phase pancreatic cancer. In embodiments, the pancreatic cancer is 1 phase pancreatic cancer. In embodiments, the pancreatic cancer is IA phase. In embodiments, the pancreatic cancer is IIB phase. In embodiments, the pancreatic cancer is 2 phase pancreatic cancer. In embodiments, the pancreatic cancer is IIA phase. In embodiments, the pancreatic cancer is IIB phase. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer or stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, or stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, stage 3 pancreatic cancer, or stage 4 pancreatic cancer.In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient and administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient and surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method comprises administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an image-based screening to the patient, administering an effective amount of an anticancer agent to the patient, and administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises administering an image-based screen to the patient and administering an effective amount of an anti-cancer agent to the patient. In embodiments, the method comprises administering an image-based screen to the patient. In embodiments, the biological sample obtained from the patient further comprises elevated expression levels of RNA relative to a control, the RNA selected from the group consisting of: cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free let-7f-5p, cell-free miR-3 exosomal miR-69-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-375-3p, exosomal miR-199a-5p, and combinations of two or more thereof.In an embodiment, the biological sample obtained from the patient further comprises elevated expression levels of a RNA relative to a control, the RNA being selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, and a combination of two or more thereof. In an embodiment, the biological sample obtained from the patient further comprises elevated expression levels of an RNA relative to a control, the RNA being selected from the group consisting of cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, and a combination of two or more thereof.
[0075] Provided herein is a method for treating pancreatic cancer in a patient in need thereof, the method comprising: (i) detecting an elevated expression level of an RNA relative to a control in a biological sample obtained from the patient, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, or a combination of two or more thereof; and (ii) administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. The elevated expression level of RNA relative to the control indicates that the patient has pancreatic cancer. Upon diagnosing the patient with pancreatic cancer, treatment is initiated by administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method comprises administering to the patient an image-based screening, administering to the patient an effective amount of an anticancer agent, and administering to the patient an effective amount of radiation therapy. In embodiments, the method comprises administering an image-based screening to the patient and administering an effective amount of an anticancer agent to the patient. In embodiments, the method comprises administering an image-based screening to the patient. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises at least three RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises at least four RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises two RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p.In embodiments, the RNA comprises three RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises four RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient suffers from new-onset diabetes. In embodiments, the patient suffers from diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient suffers from new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer or stage 2 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer. In embodiments, the pancreatic cancer is stage IA pancreatic cancer. In embodiments, the pancreatic cancer is stage IB. In embodiments, the pancreatic cancer is stage 2 pancreatic cancer. In embodiments, the pancreatic cancer is stage IIA. In embodiments, the pancreatic cancer is stage IIB. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer or stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, or stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, stage 3 pancreatic cancer, or stage 4 pancreatic cancer. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample.In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient and administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient and surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method comprises administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an image-based screening to the patient, administering an effective amount of an anticancer agent to the patient, and administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises administering an image-based screening to the patient and administering an effective amount of an anticancer agent to the patient. In embodiments, the method comprises administering an image-based screening to the patient. In embodiments, the method further comprises detecting elevated expression levels of RNA relative to a control, the RNA selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, and a combination of two or more thereof. In embodiments, the method further comprises detecting elevated expression levels of RNA relative to a control, the RNA selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, and a combination of two or more thereof. In an embodiment, the method further comprises detecting elevated expression levels of an RNA relative to a control, the RNA being selected from the group consisting of cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, and a combination of two or more thereof.
[0076] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the methods comprising: (i) detecting elevated expression levels of RNA in a biological sample obtained from the patient relative to a control, wherein the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, or a combination of two or more thereof; and (ii) administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically resecting all or part of the pancreas of the patient, or a combination of two or more thereof. Elevated expression levels of the RNA relative to the control indicate that the patient has pancreatic cancer. Upon diagnosis of pancreatic cancer in a patient, treatment is initiated by administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method comprises administering to the patient an image-based screening, administering to the patient an effective amount of an anticancer agent, and administering to the patient an effective amount of radiation therapy. In embodiments, the method comprises administering to the patient an image-based screening, and administering to the patient an effective amount of an anticancer agent. In embodiments, the method comprises administering to the patient an image-based screening. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least three RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least four RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least five RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least six RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least seven RNAs selected from the group consisting of exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises two RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises three RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes four RNAs selected from the group consisting of exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises five RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises six RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises seven RNAs selected from the group consisting of exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient suffers from diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient suffers from new-onset diabetes and is at least 50 years old. In embodiments, human patients are at least 55 years old. In embodiments, human patients are at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more of them. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, pancreatic cancer is phase 1 pancreatic cancer. In embodiments, pancreatic cancer is phase IA. In embodiments, pancreatic cancer is phase IB. In embodiments, the pancreatic cancer is stage 2 pancreatic cancer. In embodiments, the pancreatic cancer is stage IIA. In embodiments, the pancreatic cancer is stage IIB.In embodiments, the pancreatic cancer is stage 3 pancreatic cancer or stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, or stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, stage 3 pancreatic cancer, or stage 4 pancreatic cancer. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient and administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent and surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method comprises administering to the patient an effective amount of radiation therapy. In embodiments, the method comprises surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering to the patient an image-based screening, administering to the patient an effective amount of an anticancer agent, and administering to the patient an effective amount of radiation therapy. In embodiments, the method comprises administering to the patient an image-based screening, and administering to the patient an effective amount of an anticancer agent. In embodiments, the method comprises administering to the patient an image-based screening. In embodiments, the method further comprises detecting an elevated expression level of an RNA relative to a control, the RNA selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-375-3p, exosomal miR-199a-5p, and a combination of two or more thereof. In embodiments, the method further comprises detecting an elevated expression level of an RNA relative to a control, the RNA selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, and a combination of two or more thereof.In embodiments, the method further comprises detecting an elevated expression level of an RNA relative to a control, the RNA selected from the group consisting of exosomal miR-375-3p, exosomal miR-199a-5p, and a combination of two or more thereof.
[0077] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the methods comprising: (i) detecting elevated expression levels of RNA in a biological sample obtained from the patient relative to a control, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145 R-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof; and (ii) administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, surgically removing all or part of the pancreas of the patient, or a combination of two or more thereof. In embodiments, the method comprises administering an image-based screening to the patient, administering an effective amount of an anticancer agent to the patient, and administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises administering an image-based screening to the patient and administering an effective amount of an anticancer agent to the patient. In embodiments, the method comprises administering an image-based screening to the patient. In embodiments, elevated expression levels of RNA indicate that the patient has pancreatic cancer. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer or stage 2 pancreatic cancer. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level.In an embodiment, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, or a combination of two or more thereof. In embodiments, the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof. In embodiments, the control is the average expression level of the RNA in a population of healthy patients.
[0078] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the methods comprising: (i) detecting elevated expression levels of RNA in a biological sample obtained from the patient relative to a control, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-511, exosomal miR-512, exosomal miR-513, exosomal miR-514, exosomal miR-515, exosomal miR-516 R-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, or a combination of two or more thereof; and (ii) administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, surgically removing all or part of the pancreas of the patient, or a combination of two or more thereof. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least three RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least four RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least five RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least six RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least seven RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least eight RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least nine RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises at least ten RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least eleven RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a- 5p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least twelve RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a- 5p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least thirteen RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a- 5p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free miR -30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises two RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises three RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises four RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises five RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises six RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises seven RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises eight RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises nine RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises ten RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises eleven RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises twelve RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises thirteen RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA includes cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free miR In some embodiments, the patient has symptoms of pancreatic cancer. In some embodiments, the patient has new-onset diabetes. In some embodiments, the patient has diabetes. In some embodiments, the patient is at least 45 years old. In some embodiments, the patient has new-onset diabetes and is at least 50 years old. In some embodiments, the human patient is at least 55 years old. In some embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has elevated carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, e-cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer. In embodiments, the pancreatic cancer is phase IA. In embodiments, the pancreatic cancer is phase IB. In embodiments, the pancreatic cancer is phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase IIA. In embodiments, the pancreatic cancer is phase IIB. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population.In embodiments, the method comprises administering to the patient an effective amount of an anti-cancer agent, surgically removing all or part of the patient's pancreas, or a combination thereof.
[0079] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the methods comprising: (i) detecting elevated expression levels of RNA in a biological sample obtained from the patient relative to a control, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, or a combination of two or more thereof; and (ii) administering to the patient an effective amount of an anti-cancer agent, administering to the patient an effective amount of radiation therapy, surgically resecting all or part of the patient's pancreas, or a combination of two or more thereof. In an embodiment, the RNA includes at least two RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes at least three RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes at least four RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes at least five RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p.In embodiments, the RNA includes cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes two RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes three RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p and cell-free miR-23b-3p. In an embodiment, the RNA includes four RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p and cell-free miR-23b-3p. In an embodiment, the RNA includes five RNAs selected from the group consisting of: cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p and cell-free miR-23b-3p. In embodiments, the RNA comprises cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient has diabetes.In embodiments, the patient is at least 45 years old. In embodiments, the patient suffers from new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer. In embodiments, the pancreatic cancer is phase 2 pancreatic cancer. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population. In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent, surgically removing all or part of the patient's pancreas, or a combination thereof.
[0080] Provided herein are methods for treating pancreatic cancer in a patient in need thereof, the methods comprising: (i) detecting elevated expression levels of RNA in a biological sample obtained from the patient relative to a control, wherein the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3 ... , exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, or a combination of two or more thereof; and (ii) administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, surgically removing all or part of the pancreas of the patient, or a combination of two or more thereof. In embodiments, the RNA includes at least two RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least three RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA includes at least four RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least five RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least six RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least seven RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA includes at least seven RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes two RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes three RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes four RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes five RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes six RNAs selected from the group consisting of exosome miR-1260a, exosome miR-141-3p, exosome miR-143-3p, exosome miR-148a-3p, exosome miR-200c-3p, exosome miR-216a-5p, exosome miR-34a-5p, exosome miR-1260b, exosome miR-145-5p, exosome miR-200a-3p, exosome miR-200b-3p, exosome miR-216b-5p, exosome miR-217-5p, exosome miR-429, and exosome miR-145-3p. In an embodiment, the RNA includes seven RNAs selected from the group consisting of exosome miR-1260a, exosome miR-141-3p, exosome miR-143-3p, exosome miR-148a-3p, exosome miR-200c-3p, exosome miR-216a-5p, exosome miR-34a-5p, exosome miR-1260b, exosome miR-145-5p, exosome miR-200a-3p, exosome miR-200b-3p, exosome miR-216b-5p, exosome miR-217-5p, exosome miR-429, and exosome miR-145-3p.In an embodiment, the RNA includes seven RNAs selected from the group consisting of exosome miR-1260a, exosome miR-141-3p, exosome miR-143-3p, exosome miR-148a-3p, exosome miR-200c-3p, exosome miR-216a-5p, exosome miR-34a-5p, exosome miR-1260b, exosome miR-145-5p, exosome miR-200a-3p, exosome miR-200b-3p, exosome miR-216b-5p, exosome miR-217-5p, exosome miR-429, and exosome miR-145-3p. In embodiments, the RNA comprises exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient has diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient suffers from new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer. In embodiments, the pancreatic cancer is phase IA. In embodiments, the pancreatic cancer is phase IB. In embodiments, the pancreatic cancer is phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is stage IIA. In embodiments, the pancreatic cancer is stage IIB. In embodiments, the biological sample obtained from the patient has normal CA19-9 levels. In embodiments, the biological sample obtained from the patient has elevated CA19-9 levels.In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of the RNA in a population of healthy patients. In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent, surgically removing all or part of the patient's pancreas, or a combination thereof.
[0081] Diagnostic methods
[0082] Provided herein is a method for diagnosing a patient with pancreatic cancer, the method comprising detecting elevated expression levels of RNA relative to a control in a biological sample obtained from the patient, thereby diagnosing the patient with pancreatic cancer; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, or a combination of two or more thereof. Elevated expression levels of the RNA relative to the control indicate that the patient has pancreatic cancer. In an embodiment, an elevated expression level of RNA relative to a control indicates that the patient may have pancreatic cancer. Upon diagnosis of pancreatic cancer in a patient, treatment is initiated by administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least five RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least six RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least seven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least eight RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least nine RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least ten RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least eleven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least twelve RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes two RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes five RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes six RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes seven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes eight RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes nine RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes ten RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes eleven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes twelve RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient has diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient has new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is 1 phase pancreatic cancer or 2 phase pancreatic cancer. In embodiments, the pancreatic cancer is 1 phase pancreatic cancer. In embodiments, the pancreatic cancer is IA phase. In embodiments, the pancreatic cancer is IIB phase. In embodiments, the pancreatic cancer is 2 phase pancreatic cancer. In embodiments, the pancreatic cancer is IIA phase. In embodiments, the pancreatic cancer is IIB phase. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer or stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, or stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, stage 3 pancreatic cancer, or stage 4 pancreatic cancer.In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient and administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient and surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method comprises administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an image-based screening to the patient, administering an effective amount of an anticancer agent to the patient, and administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises administering an image-based screen to the patient and administering an effective amount of an anti-cancer agent to the patient. In embodiments, the method comprises administering an image-based screen to the patient. In embodiments, the method further comprises detecting elevated expression levels of an RNA selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-137a-5p, cell-free miR-138b-5p, cell-free miR-139b-5p, cell-free miR-240c-5p, cell-free miR-251d-5p, cell-free miR-252d-5p, cell-free miR-253d-5p, cell-free miR-254d-5p, cell-free miR-255d-5p, cell-free miR-256d-5p, cell-free miR-257d-5p, cell-free miR-258d-5p, cell-free miR-259d-5p, cell-free miR-259d-5p, cell-free miR-251d-5p, cell-free miR-257d-5p, cell-free miR-259d-5p, cell-free miR-25 exosomal miR-495-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-375-3p, exosomal miR-199a-5p, and a combination of two or more thereof.In embodiments, the method further comprises detecting elevated expression levels of an RNA relative to a control, the RNA selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, and a combination of two or more thereof. In embodiments, the method further comprises detecting elevated expression levels of an RNA relative to a control, the RNA being selected from the group consisting of cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, and a combination of two or more thereof.
[0083] Provided herein is a method for diagnosing a patient with pancreatic cancer, the method comprising detecting elevated expression levels of RNA relative to a control in a biological sample obtained from the patient, thereby diagnosing the patient with pancreatic cancer; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, or a combination of two or more thereof. Elevated expression levels of RNA relative to the control indicate that the patient has pancreatic cancer. In embodiments, elevated expression levels of RNA relative to the control indicate that the patient may have pancreatic cancer. Elevated expression levels of RNA relative to the control indicate that the patient may have pancreatic cancer. Elevated expression levels of RNA relative to the control indicate that the patient has pancreatic cancer. In embodiments, elevated expression levels of RNA relative to the control indicate that the patient may have pancreatic cancer. Upon diagnosis of pancreatic cancer in the patient, treatment is initiated by administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises at least three RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises at least four RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises two RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p.In embodiments, the RNA comprises four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient has diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient has new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has elevated carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer. In embodiments, the pancreatic cancer is phase IA. In embodiments, the pancreatic cancer is phase IB. In embodiments, the pancreatic cancer is phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase IIA. In embodiments, the pancreatic cancer is phase IIB. In embodiments, the pancreatic cancer is phase 3 pancreatic cancer or phase 4 pancreatic cancer. In embodiments, pancreatic cancer is stage 3 pancreatic cancer. In embodiments, pancreatic cancer is stage 4 pancreatic cancer. In embodiments, pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer or stage 3 pancreatic cancer. In embodiments, pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, stage 3 pancreatic cancer or stage 4 pancreatic cancer. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population. In embodiments, the method further comprises administering an effective amount of an anticancer agent to the patient.In embodiments, the method further comprises administering to the patient an effective amount of an anticancer agent and administering to the patient an effective amount of radiation therapy. In embodiments, the method further comprises administering to the patient an effective amount of an anticancer agent and surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method further comprises administering to the patient an effective amount of radiation therapy. In embodiments, the method further comprises surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method further comprises administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, and surgically removing all or part of the patient's pancreas ... image-based screening, administering to the patient an effective amount of an anticancer agent, and administering to the patient an effective amount of radiation therapy. In embodiments, the method further comprises administering to the patient an image-based screening, administering to the patient an effective amount of an anticancer agent, and administering to the patient an effective amount of radiation therapy. In embodiments, the method further comprises administering to the patient an image-based screening, and administering to the patient an effective amount of an anticancer agent. In embodiments, the method further comprises administering to the patient an image-based screening. In embodiments, the method further comprises detecting elevated expression levels of RNA relative to a control, the RNA selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, and a combination of two or more thereof. In embodiments, the method further comprises detecting elevated expression levels of RNA relative to a control, the RNA selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, and a combination of two or more thereof. In an embodiment, the method further comprises detecting elevated expression levels of an RNA relative to a control, the RNA being selected from the group consisting of cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, and a combination of two or more thereof.
[0084] Provided herein is a method for diagnosing a patient with pancreatic cancer, the method comprising detecting elevated expression levels of RNA relative to a control in a biological sample obtained from the patient, thereby diagnosing the patient with pancreatic cancer; wherein the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, or a combination of two or more thereof. Elevated expression levels of RNA relative to the control indicate that the patient has pancreatic cancer. In embodiments, elevated expression levels of RNA relative to the control indicate that the patient may have pancreatic cancer. Upon diagnosis of pancreatic cancer in the patient, treatment may be initiated by administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least three RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least four RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least five RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least six RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least seven RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises two RNAs selected from the group consisting of exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises three RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises four RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes five RNAs selected from the group consisting of exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises six RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises seven RNAs selected from the group consisting of: exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient has diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient has new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the patient has diabetes (e.g., new-onset diabetes or pre-existing diabetes), has obesity, has elevated carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer. In embodiments, the pancreatic cancer is phase IA. In embodiments, the pancreatic cancer is phase IB. In embodiments, the pancreatic cancer is phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase IIA. In embodiments, the pancreatic cancer is phase IIB. In embodiments, the pancreatic cancer is phase 3 pancreatic cancer or phase 4 pancreatic cancer. In embodiments, the pancreatic cancer is phase 3 pancreatic cancer. In embodiments, the pancreatic cancer is phase 4 pancreatic cancer. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer, phase 2 pancreatic cancer, or phase 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, stage 3 pancreatic cancer, or stage 4 pancreatic cancer.In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population. In embodiments, the method further comprises administering an effective amount of an anticancer agent to the patient. In embodiments, the method further comprises administering an effective amount of an anticancer agent to the patient and administering an effective amount of radiotherapy to the patient. In embodiments, the method further comprises administering an effective amount of an anticancer agent to the patient and surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method further comprises administering an effective amount of radiotherapy to the patient. In embodiments, the method further comprises administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiotherapy to the patient, and surgically removing all or part of the patient's pancreas. In embodiments, the method further comprises administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiotherapy to the patient, and surgically removing all or part of the patient's pancreas. In embodiments, the method further comprises detecting an elevated expression level of an RNA relative to a control, the RNA selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-375-3p, exosomal miR-199a-5p, and a combination of two or more thereof. In embodiments, the method further comprises detecting an elevated expression level of an RNA relative to a control, the RNA being selected from the group consisting of: exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, and a combination of two or more thereof. In embodiments, the method further comprises detecting an elevated expression level of an RNA relative to a control, the RNA being selected from the group consisting of: exosomal miR-375-3p, exosomal miR-199a-5p, and a combination of two or more thereof.
[0085] Provided herein is a method for diagnosing a patient with pancreatic cancer, the method comprising detecting elevated expression levels of RNA relative to a control in a biological sample obtained from the patient, thereby diagnosing the patient with pancreatic cancer; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, exosomal ...23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-23b-3p, exosomal miR-23b-3p, exosomal miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-23b-3p, exosomal miR-23b-3 In some embodiments, the elevated expression level of the miR-117a-5p, miR-117b-5p, miR-117c-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p, miR-117d-5p In embodiments, the method further comprises administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method further comprises administering to the patient an effective amount of an anticancer agent. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer or stage 2 pancreatic cancer. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In an embodiment, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, or a combination of two or more thereof.In embodiments, the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof. In embodiments, the control is the average expression level of the RNA in a population of healthy patients.
[0086] Provided herein is a method for diagnosing a patient with pancreatic cancer, the method comprising detecting elevated expression levels of RNA in a biological sample obtained from the patient relative to a control, thereby diagnosing the patient with pancreatic cancer; the RNA comprising cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b -5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, or a combination of two or more thereof. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least three RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least four RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least five RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least six RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least seven RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least eight RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least nine RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises at least ten RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least eleven RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a- 5p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least twelve RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a- 5p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least thirteen RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a- 5p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free miR -30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises two RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises three RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises four RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises five RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises six RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises seven RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises eight RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises nine RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises ten RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p , cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises eleven RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA comprises twelve RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA comprises thirteen RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5 p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA includes cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free miR In some embodiments, the patient has symptoms of pancreatic cancer. In some embodiments, the patient has new-onset diabetes. In some embodiments, the patient has diabetes. In some embodiments, the patient is at least 45 years old. In some embodiments, the patient has new-onset diabetes and is at least 50 years old. In some embodiments, the human patient is at least 55 years old. In some embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has elevated carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, e-cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer. In embodiments, the pancreatic cancer is phase IA. In embodiments, the pancreatic cancer is phase IB. In embodiments, the pancreatic cancer is phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase IIA. In embodiments, the pancreatic cancer is phase IIB. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population.In embodiments, the method comprises administering to the patient an effective amount of an anti-cancer agent, surgically removing all or part of the patient's pancreas, or a combination thereof.
[0087] Provided herein is a method for diagnosing a patient with pancreatic cancer, the method comprising detecting elevated expression levels of RNA relative to a control in a biological sample obtained from the patient, thereby diagnosing the patient with pancreatic cancer; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, or a combination of two or more thereof. In an embodiment, the RNA includes at least two RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes at least three RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes at least four RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes at least five RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p.In embodiments, the RNA includes cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes two RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In an embodiment, the RNA includes three RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p and cell-free miR-23b-3p. In an embodiment, the RNA includes four RNAs selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p and cell-free miR-23b-3p. In an embodiment, the RNA includes five RNAs selected from the group consisting of: cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p and cell-free miR-23b-3p. In embodiments, the RNA comprises cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient has diabetes.In embodiments, the patient is at least 45 years old. In embodiments, the patient suffers from new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer. In embodiments, the pancreatic cancer is phase 2 pancreatic cancer. In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population. In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent, surgically removing all or part of the patient's pancreas, or a combination thereof.
[0088] Provided herein is a method for diagnosing a patient with pancreatic cancer, the method comprising detecting elevated expression levels of RNA relative to a control in a biological sample obtained from the patient, thereby diagnosing the patient with pancreatic cancer; wherein the RNA comprises exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, or a combination of two or more thereof. In embodiments, the RNA includes at least two RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least three RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA includes at least four RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least five RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least six RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes at least seven RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA includes at least seven RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes two RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes three RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes four RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes five RNAs selected from the group consisting of exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes six RNAs selected from the group consisting of exosome miR-1260a, exosome miR-141-3p, exosome miR-143-3p, exosome miR-148a-3p, exosome miR-200c-3p, exosome miR-216a-5p, exosome miR-34a-5p, exosome miR-1260b, exosome miR-145-5p, exosome miR-200a-3p, exosome miR-200b-3p, exosome miR-216b-5p, exosome miR-217-5p, exosome miR-429, and exosome miR-145-3p. In an embodiment, the RNA includes seven RNAs selected from the group consisting of exosome miR-1260a, exosome miR-141-3p, exosome miR-143-3p, exosome miR-148a-3p, exosome miR-200c-3p, exosome miR-216a-5p, exosome miR-34a-5p, exosome miR-1260b, exosome miR-145-5p, exosome miR-200a-3p, exosome miR-200b-3p, exosome miR-216b-5p, exosome miR-217-5p, exosome miR-429, and exosome miR-145-3p.In an embodiment, the RNA includes seven RNAs selected from the group consisting of exosome miR-1260a, exosome miR-141-3p, exosome miR-143-3p, exosome miR-148a-3p, exosome miR-200c-3p, exosome miR-216a-5p, exosome miR-34a-5p, exosome miR-1260b, exosome miR-145-5p, exosome miR-200a-3p, exosome miR-200b-3p, exosome miR-216b-5p, exosome miR-217-5p, exosome miR-429, and exosome miR-145-3p. In embodiments, the RNA comprises exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient has diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient suffers from new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer or phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is phase 1 pancreatic cancer. In embodiments, the pancreatic cancer is phase IA. In embodiments, the pancreatic cancer is phase IB. In embodiments, the pancreatic cancer is phase 2 pancreatic cancer. In embodiments, the pancreatic cancer is stage IIA. In embodiments, the pancreatic cancer is stage IIB. In embodiments, the biological sample obtained from the patient has normal CA19-9 levels. In embodiments, the biological sample obtained from the patient has elevated CA19-9 levels.In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of the RNA in a population of healthy patients. In embodiments, the method comprises administering to the patient an effective amount of an anticancer agent, surgically removing all or part of the patient's pancreas, or a combination thereof.
[0089] Monitoring methods
[0090] Provided herein are methods for monitoring a patient at risk of developing pancreatic cancer, the methods comprising: (i) detecting the expression level of an RNA in a biological sample obtained from the patient at a first time point; (ii) detecting the expression level of an RNA in a biological sample obtained from the patient at a second time point, wherein the second time point is later than the first time point; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-23 ...3b-3p, exosom exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a ...260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-148a-3p, exosomal miR-148a-3p, exosomal miR-148a-3p, exosomal miR-148a-3p, exosomal miR-148a-3p, exosomal miR-148a-3p, exosomal miR-148a-3p, exosomal miR-14 iR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof.Provided herein is a method for monitoring a patient at risk of developing pancreatic cancer, the method comprising: (i) detecting the expression level of RNA in a biological sample obtained from the patient at a first time point; (ii) detecting the expression level of RNA in a biological sample obtained from the patient at a second time point, wherein the second time point is later than the first time point; the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-335-5 ... exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, or a combination of two or more thereof. Provided herein are methods for monitoring a patient at risk of developing pancreatic cancer, the methods comprising: (i) detecting the expression level of RNA in a biological sample obtained from the patient at a first time point; (ii) detecting the expression level of RNA in a biological sample obtained from the patient at a second time point, wherein the second time point is later than the first time point; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, or a combination of two or more thereof. In embodiments, the expression level of the RNA at the second time point is elevated when compared to the expression level of the RNA at the first time point. In embodiments, the elevated expression level of the RNA at the second time point, when compared to the expression level of the RNA at the first time point, indicates that the patient has an increased risk of developing pancreatic cancer or has developed pancreatic cancer. In embodiments, the expression level of the RNA at the second time point is approximately the same as the expression level of the RNA at the first time point.In embodiments, the expression level of the RNA at the second time point that is approximately the same as the expression level of the RNA at the first time point indicates that the patient does not have the risk of increased development pancreatic cancer. In embodiments, the second time point is about 6 months after the first time point. In embodiments, the second time point is about 1 year after the first time point. In embodiments, the second time point is about 18 months after the first time point. In embodiments, the second time point is about 2 years after the first time point. In embodiments, the method of repeating monitoring the patient once every 6 months, once a year, once every 18 months, once every two years, once every three years, once every four years or once every five years. In embodiments, the patient is at risk of developing pancreatic cancer. In embodiments, the patient suffers from diabetes (for example, new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, ≥40 years old, smokes, has a history of smoking or a combination of two or more thereof. In embodiments, the patient is at risk of developing pancreatic cancer. In embodiments, the patient suffers from diabetes. In embodiments, the patient suffers from new-onset diabetes. In embodiments, the patient suffers from pre-existing diabetes. In embodiments, the diabetes is type 2 diabetes. In embodiments, the patient suffers from obesity. In embodiments, the patient has elevated carbohydrate antigen 19-9 levels. In embodiments, the patient has a family history of pancreatic cancer. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient is ≥40 years old. In embodiments, the patient smokes. In embodiments, the patient has a history of smoking. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least five RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least six RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least seven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least eight RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least nine RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least ten RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least eleven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least twelve RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes two RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes five RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes six RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes seven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes eight RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes nine RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes ten RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes eleven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes twelve RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the biological sample obtained from the patient has normal CA19-9 levels. In embodiments, the biological sample obtained from the patient has elevated CA19-9 levels. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a population of healthy patients. In embodiments, the method further comprises administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the patient's pancreas, or a combination of two or more thereof.
[0091] Detection method
[0092] Provided herein are methods for detecting RNA biomarkers in a patient having or suspected of having pancreatic cancer, the methods comprising detecting elevated expression levels of RNA in a biological sample obtained from the patient relative to a control, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, or a combination of two or more thereof; and wherein the RNA comprises an RNA biomarker. In embodiments, the patient has pancreatic cancer. In embodiments, the patient is suspected of having pancreatic cancer. Elevated expression levels of the RNA relative to a control indicate that the patient has pancreatic cancer. In embodiments, elevated expression levels of the RNA relative to a control indicate that the patient may have pancreatic cancer. In embodiments, the method further comprises administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least five RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least six RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least seven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least eight RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least nine RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least ten RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises at least eleven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In embodiments, the RNA comprises at least twelve RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA includes cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes two RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes five RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes six RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes seven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes eight RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes nine RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes ten RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In an embodiment, the RNA includes eleven RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p.In an embodiment, the RNA includes twelve RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, and exosomal miR-145-3p. In embodiments, the patient has symptoms of pancreatic cancer. In embodiments, the patient has new-onset diabetes. In embodiments, the patient has diabetes. In embodiments, the patient is at least 45 years old. In embodiments, the patient has new-onset diabetes and is at least 50 years old. In embodiments, the human patient is at least 55 years old. In embodiments, the human patient is at least 60 years old. In embodiments, the patient suffers from diabetes (e.g., new-onset diabetes or pre-existing diabetes), suffers from obesity, has rising carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof. In embodiments, the patient suffers from obesity. In embodiments, the patient smokes nicotine (e.g., cigarettes, cigars, electronic cigarettes) or has a history of smoking nicotine. In embodiments, the patient has a history of pancreatitis. In embodiments, the patient has a history of chronic pancreatitis. In embodiments, the pancreatic cancer is pancreatic ductal adenocarcinoma. In embodiments, the pancreatic cancer is 1 phase pancreatic cancer or 2 phase pancreatic cancer. In embodiments, the pancreatic cancer is 1 phase pancreatic cancer. In embodiments, the pancreatic cancer is IA phase. In embodiments, the pancreatic cancer is IIB phase. In embodiments, the pancreatic cancer is 2 phase pancreatic cancer. In embodiments, the pancreatic cancer is IIA phase. In embodiments, the pancreatic cancer is IIB phase. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer or stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 4 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, or stage 3 pancreatic cancer. In embodiments, the pancreatic cancer is stage 1 pancreatic cancer, stage 2 pancreatic cancer, stage 3 pancreatic cancer, or stage 4 pancreatic cancer.In embodiments, the biological sample obtained from the patient has a normal CA19-9 level. In embodiments, the biological sample obtained from the patient has an elevated CA19-9 level. In embodiments, the biological sample obtained from the patient is Lewis antigen negative. In embodiments, the biological sample is a blood sample. In embodiments, the blood sample is a serum sample. In embodiments, the blood sample is a plasma sample. In embodiments, the control is the average expression level of RNA in a healthy patient population. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient and administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient and surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the method comprises administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an effective amount of an anticancer agent to the patient, administering an effective amount of radiation therapy to the patient, and surgically removing all or part of the patient's pancreas. In embodiments, the method comprises administering an image-based screening to the patient, administering an effective amount of an anticancer agent to the patient, and administering an effective amount of radiation therapy to the patient. In embodiments, the method comprises administering an image-based screen to the patient and administering an effective amount of an anti-cancer agent to the patient. In embodiments, the method comprises administering an image-based screen to the patient. In embodiments, the method further comprises detecting elevated expression levels of an RNA selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-137a-5p, cell-free miR-138b-5p, cell-free miR-139b-5p, cell-free miR-240c-5p, cell-free miR-251d-5p, cell-free miR-252d-5p, cell-free miR-253d-5p, cell-free miR-254d-5p, cell-free miR-255d-5p, cell-free miR-256d-5p, cell-free miR-257d-5p, cell-free miR-258d-5p, cell-free miR-259d-5p, cell-free miR-259d-5p, cell-free miR-251d-5p, cell-free miR-257d-5p, cell-free miR-259d-5p, cell-free miR-25 exosomal miR-495-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, exosomal miR-375-3p, exosomal miR-199a-5p, and a combination of two or more thereof.In embodiments, the method further comprises detecting elevated expression levels of an RNA relative to a control, the RNA selected from the group consisting of cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, and a combination of two or more thereof. In embodiments, the method further comprises detecting elevated expression levels of an RNA relative to a control, the RNA being selected from the group consisting of cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, and a combination of two or more thereof.
[0093] Provided herein are methods for detecting RNA biomarkers in a patient having or suspected of having pancreatic cancer, the method comprising detecting elevated expression levels of RNA relative to a control in a biological sample obtained from the patient, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, or a combination of two or more thereof; and wherein the RNA is an RNA biomarker. In embodiments, the patient has pancreatic cancer. In embodiments, the patient is suspected of having pancreatic cancer. Elevated expression levels of RNA relative to a control indicate that the patient has pancreatic cancer. In embodiments, elevated expression levels of RNA relative to a control indicate that the patient may have pancreatic cancer. In embodiments, the method further comprises administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, surgically removing all or part of the patient's pancreas, or a combination of two or more thereof. In embodiments, the RNA comprises at least two RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises at least three RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises at least four RNAs selected from the group consisting of: cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises two RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p. In embodiments, the RNA comprises three RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, and cell-free miR-23b-3p.In embodiments, the RNA comprises four RNAs selected from the group consisting of cell-free miR-30c-5p, cell-free miR-142-3p, c...
Claims
1. A method for detecting RNA biomarkers in a patient having or suspected of having pancreatic cancer, the method comprising detecting elevated expression levels of RNA in a biological sample obtained from the patient relative to a control, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p. p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof.
2. A method for treating pancreatic cancer in a patient in need thereof, the method comprising administering to the patient an effective amount of an anticancer agent, administering to the patient an effective amount of radiation therapy, administering to the patient an image-based screening, surgically removing all or part of the pancreas of the patient, or a combination of two or more thereof; wherein the biological sample obtained from the patient comprises an elevated expression level of an RNA relative to a control; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3 p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof.
3. A method of treating pancreatic cancer in a patient in need thereof, the method comprising: (i) detecting the expression level of an RNA that is elevated in a biological sample obtained from a patient relative to a control, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof; (ii) administering to the patient an effective amount of an anti-cancer agent, administering to the patient an effective amount of radiation therapy, administering to the patient image-based screening, surgically removing all or part of the pancreas of the patient, or a combination of two or more thereof.
4. A method for diagnosing a patient with pancreatic cancer, the method comprising detecting an elevated expression level of RNA in a biological sample obtained from the patient relative to a control, thereby diagnosing the patient with pancreatic cancer; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p. p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof.
5. A method of monitoring a patient at risk of developing pancreatic cancer, the method comprising: (i) detecting the expression level of RNA in a biological sample obtained from the patient at a first time point; (ii) detecting the expression level of RNA in a biological sample obtained from the patient at a second time point, wherein the second time point is later than the first time point; The RNAs include cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof.
6. The method of claim 5, wherein an elevated expression level of the RNA at the second time point, when compared to the expression level of the RNA at the first time point, indicates that the patient has an increased risk of developing pancreatic cancer.
7. The method of claim 1, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR -429, exosomal miR-145-3p, cell-free let-7e-5p, cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, or a combination of two or more thereof.
8. The method of claim 1, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, or a combination of two or more thereof.
9. The method of claim 1, wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p and cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429 and exosomal miR-145-3p.
10. The method of claim 1, wherein the RNA consists of: Cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p and cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429 and exosomal miR-145-3p.
11. The method of claim 1, further comprising detecting the level of carbohydrate antigen 19-9 (CA19-9) in the biological sample obtained from the patient.
12. The method of claim 1, wherein the biological sample obtained from the patient is Lewis antigen negative.
13. The method of claim 1, wherein the biological sample is a blood sample.
14. The method of claim 1, wherein the patient has new-onset diabetes, has pre-existing diabetes, is obese, has elevated carbohydrate antigen 19-9 levels, has a family history of pancreatic cancer, has a history of pancreatitis, is ≥40 years old, smokes, has a history of smoking, or a combination of two or more thereof.
15. The method of claim 1, further comprising administering to the patient an effective amount of the anti-cancer agent.
16. The method of claim 15, wherein the anticancer agent comprises everolimus, erlotinib, olaparib, mitomycin, sunitinib, gemcitabine, 5-fluorouracil, irinotecan, oxaliplatin, paclitaxel, capecitabine, cisplatin, docetaxel, or a combination of two or more thereof.
17. The method of claim 15, wherein the anticancer agent is a chemotherapeutic agent.
18. The method of claim 17, wherein the chemotherapeutic agent comprises gemcitabine, 5-fluorouracil, irinotecan, oxaliplatin, paclitaxel, capecitabine, cisplatin, docetaxel, or a combination of two or more thereof.
19. The method of claim 17, wherein the chemotherapeutic agent is an alkylating agent, an antimetabolite compound, an anthracycline compound, an antitumor antibiotic, a platinum compound, a topoisomerase inhibitor, a vinca alkaloid, a taxane compound, an epothilone compound, or a combination of two or more thereof.
20. A kit comprising a reagent capable of detecting the expression level of RNA from a biological sample; wherein the RNA comprises cell-free miR-30c-5p, cell-free miR-142-3p, cell-free miR-340-5p, cell-free miR-335-5p, cell-free miR-23b-3p, exosomal miR-1260b, exosomal miR-145-5p, exosomal miR-200a-3p, exosomal miR-200b-3p, exosomal miR-216b-5p, exosomal miR-217-5p, exosomal miR-429, exosomal miR-145-3p, cell-free let-7e-5p, Cell-free miR-26a-5p, cell-free miR-223-3p, cell-free miR-340-3p, exosomal miR-1260a, exosomal miR-141-3p, exosomal miR-143-3p, exosomal miR-148a-3p, exosomal miR-200c-3p, exosomal miR-216a-5p, exosomal miR-34a-5p, cell-free let-7f-5p, cell-free miR-369-3p, cell-free miR-125a-5p, cell-free miR-495-3p, exosomal miR-375-3p, exosomal miR-199a-5p, or a combination of two or more thereof.