Composition for diagnosis of radiation resistance of colorectal cancer or prognosis of colorectal cancer

Abstract

In the invention, mRNA of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes, or proteins coded by the genes, show different expression levels between radiation-resistant colorectal cancer cells and radiation-sensitive colorectal cancer cells, and are closely related to the reduction of the survival rate in colorectal cancer patients. Therefore, according to the present invention, an agent for measuring the expression level of mRNA of a gene selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4 or a protein encoded by the gene effectively diagnoses radiation resistance in colorectal cancer or predicts radiation therapy for colorectal cancer. This makes it possible to determine whether to perform radiation therapy and the optimal radiation dose, thereby improving the efficiency and outcome of radiation therapy for colorectal cancer.

Description

Cross-reference to related applications

[0001] This application claims the benefit of priority to Korean Patent Application No. 10-2023-0112012, filed on August 25, 2023, with the Korean Intellectual Property Office, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This disclosure relates to radioresistant compositions for the diagnosis of colorectal cancer and their applications. Background Technology

[0003] Cancer treatments include surgery, chemotherapy, and radiation therapy, with radiation therapy gaining increasing importance recently. Cases have been reported where radiation therapy alone has been effective in treating tumors when surgery is difficult, and the use of radiation in cancer treatment is evolving annually. Therefore, radiation therapy has been established as an effective method for treating tumors without causing significant pain or resistance in patients. It is estimated that approximately 30% to 50% of cancer patients receive radiation therapy at some point during their treatment. Because the number of cancer patients receiving radiation therapy each year continues to increase, its importance in cancer treatment is also growing.

[0004] Radiation therapy is typically used either alone or in combination with chemotherapy to treat various types of cancer. However, the effectiveness of radiation therapy varies depending on the characteristics of the cancer, the patient, and whether radiation is combined with other treatments. Commonly used cancers for which radiation therapy is widely administered include cervical cancer, pharyngeal cancer, lung cancer, brain cancer, and breast cancer. While these types of cancer are primary targets for radiation therapy, adverse reactions to radiation therapy occur frequently, necessitating measures to improve treatment efficiency. Furthermore, although radiation therapy can be performed smoothly and show good initial responses, recurrence is common; therefore, developing strategies for dealing with recurrent cancers is also important for improving the effectiveness of radiation therapy.

[0005] Furthermore, it has been pointed out that the radiation resistance acquired by cancer cells and damage to normal tissues during high-dose radiotherapy are problems that reduce the efficiency of radiotherapy. Therefore, research is needed to improve the efficiency of radiotherapy. Currently, radiotherapy, along with surgery or chemotherapy, is an effective treatment for cancer and is used to kill cancer cells by applying radiation to the patient's cancerous tissue.

[0006] Although cancer cells vary in their sensitivity to radiation therapy, by developing technologies that can predict an individual's sensitivity to radiation before radiation therapy, it will be possible to treat cancer by adjusting the radiation dose to each individual, thereby providing the most appropriate radiation therapy for each patient.

[0007] Meanwhile, research on companion diagnostics has been actively conducted in recent years. Companion diagnostics refer to approved diagnoses that, based on systematic analysis of individual patient factors, can help select appropriate targeted anticancer drugs and treatments. Because companion diagnostics, based on physician diagnoses, can provide clear clinical evidence for prescriptions and recommend appropriate treatments for patients, they can not only improve the efficiency of cancer treatment but also reduce the misuse or overuse of targeted anticancer drugs, thereby contributing to the financial soundness of the national health insurance system. Currently, the companion diagnostics market is growing in treatment areas such as breast cancer, lung cancer, colorectal cancer, gastric cancer, and melanoma, with particularly strong growth potential in breast cancer and lung cancer.

[0008] Korean Patent Application No. 10-2018-0143493 discloses a technique for measuring the expression level of PMVK protein or mRNA to use it for diagnosing radioresistant lung cancer or pancreatic cancer, but does not provide any data on colorectal cancer cell specificity.

[0009] In addition, Korean Patent Application No. 10-2018-0153659 discloses a technique for diagnosing the radioresistance of cancer cells by measuring the expression level of the ROMO1 gene or protein, but does not suggest a technique for more accurately diagnosing radioresistant colorectal cancer by using multiple biomarkers.

[0010] Against this backdrop, the inventors of this disclosure have studied radioresistance biomarkers and discovered novel biomarkers for diagnosing radioresistant colorectal cancer. Because these biomarkers can predict the prognosis of radioresistance or radiotherapy, they hold promise for useful application in the treatment of colorectal cancer.

[0011] [Existing Technical Documents] [Patent Literature] Korean Patent Application No. 10-2018-0143493 Korean Patent Application No. 10-2018-0153659 Summary of the Invention Technical issues One aspect of this disclosure provides a radioresistant composition for diagnosing colorectal cancer.

[0012] One aspect of this disclosure also provides a kit for diagnosing radioresistance in colorectal cancer.

[0013] One aspect of this disclosure also provides a method for providing information on radioresistance for diagnosing colorectal cancer.

[0014] One aspect of this disclosure also provides a composition for predicting the prognosis of radiotherapy for colorectal cancer.

[0015] One aspect of this disclosure also provides a kit for predicting the prognosis of radiotherapy for colorectal cancer.

[0016] One aspect of this disclosure also provides a method for providing information on the prognosis of radiotherapy for colorectal cancer.

[0017] Technical solution To achieve the above objectives, one aspect of this disclosure provides a composition for diagnosing radioresistance in colorectal cancer, comprising reagents for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4, or the expression level of proteins encoded by two or more genes.

[0018] Furthermore, another aspect of this disclosure provides a kit for diagnosing radioresistance in colorectal cancer, comprising a composition for diagnosing radioresistance in colorectal cancer.

[0019] Furthermore, another aspect of this disclosure provides a method for providing information on radioresistance in the diagnosis of colorectal cancer, the method comprising: (a) measuring the expression level of mRNA or the expression level of proteins encoded by two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 in a sample isolated from a subject; and (b) comparing the expression level of the mRNA or protein with the expression level of the mRNA or protein in a normal control group.

[0020] Furthermore, another aspect of this disclosure provides a composition for predicting the prognosis of radiotherapy for colorectal cancer, the composition comprising reagents for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes, or the expression level of proteins encoded by two or more of these genes.

[0021] Furthermore, another aspect of this disclosure provides a kit for predicting the prognosis of radiotherapy for colorectal cancer, comprising a composition for predicting the prognosis of radiotherapy for colorectal cancer. Another aspect of this disclosure provides a method for providing information predicting the prognosis of radiotherapy for colorectal cancer, comprising: (a) measuring the expression level of mRNA or the expression level of proteins encoded by two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4 isolated from a sample of a subject; and (b) comparing the expression level of the mRNA or protein with the expression level of the mRNA or protein in a normal control group.

[0022] The present invention will now be described in detail.

[0023] 1. Compositions for diagnosing radioresistance in colorectal cancer or predicting the prognosis of radiotherapy for colorectal cancer. One aspect of this disclosure provides a radioresistant composition for diagnosing colorectal cancer.

[0024] Furthermore, another aspect of this disclosure provides a composition for predicting the prognosis of radiotherapy for colorectal cancer.

[0025] The composition for diagnosing radioresistance in colorectal cancer according to this disclosure comprises, as an active ingredient, a reagent for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4, or the expression level of proteins encoded by two or more of the genes.

[0026] In addition, the composition for predicting the prognosis of radiotherapy for colorectal cancer according to this disclosure comprises, as an active ingredient, a reagent for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4, or the expression level of proteins encoded by two or more genes.

[0027] CXCL5 (CXC motif chemokine ligand 5, NCBI gene ID: 6374) is a small cytokine belonging to the CXC chemokine family. It is produced in response to the inflammatory cytokines interleukin-1 and tumor necrosis factor-α, and is known to regulate neutrophil homeostasis by inhibiting type II interferon-γ.

[0028] In this disclosure, CXCL5 protein refers not only to the wild-type CXCL5 protein consisting of the amino acid sequence of SEQ ID No: 1, but also to equivalents that have the same or similar functions or activities as the wild-type CXCL5 protein, even though their sequence portions differ, and equivalents may include amino acid sequences that have about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more sequence homology with the amino acid sequence of SEQ ID No: 1.

[0029] Cluster of Differentiation 68 (CD68) (NCBI Gene ID: 968) is a protein expressed in monocyte lineage cells and macrophages, and is generally known as a scavenger receptor that clears cell debris, promotes phagocytosis, and mediates macrophage recruitment and activation.

[0030] In this disclosure, CD68 protein refers not only to wild-type CD68 consisting of the amino acid sequence of SEQ ID No: 2, but also to equivalents that have the same or similar functions or activities as wild-type CD68 protein, even though their sequence portions differ, and equivalents may include amino acid sequences that have about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more sequence homology with the amino acid sequence of SEQ ID No: 2.

[0031] Matrilin 1 (MATN1) (NCBI gene ID: 4146) is a cartilage matrix protein involved in the formation of filamentous networks in the extracellular matrix of various tissues, and mutations in this gene are known to be associated with a variety of hereditary chondrodysplasia.

[0032] In this disclosure, MATN1 protein refers not only to the wild-type MATN1 protein composed of the amino acid sequence of SEQ ID No: 3, but also to equivalents that have the same or similar functions or activities as the wild-type MATN1 protein, even though their sequence portions are different, and equivalents may include amino acid sequences that have about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more sequence homology with the amino acid sequence of SEQ ID No: 3.

[0033] Serpin family G member 1 (NCBI gene ID: 710) is a protease inhibitor belonging to the serine protease superfamily. It is also known as C1 esterase inhibitor (C1-INH) and is known to regulate physiological pathways including complement activation, blood coagulation, fibrinolysis, and kinin production by inhibiting the activation of the C1 complex.

[0034] In this disclosure, SERPING1 protein refers not only to the wild-type SERPING1 protein consisting of the amino acid sequence of SEQ ID No: 4, but also to equivalents that have the same or similar functions or activities as the wild-type SERPING1 protein, even though their sequence portions differ, and equivalents may include amino acid sequences that have about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more sequence homology with the amino acid sequence of SEQ ID No: 4.

[0035] SNCG (γ-synuclein, NCBI gene ID: 6623) is a synuclein family protein that is associated with the pathogenesis of neurodegenerative diseases and is known to be highly correlated with breast cancer development because its overexpression is frequently observed in breast cancer cells.

[0036] In this disclosure, SNCG protein refers not only to wild-type SNCG protein composed of the amino acid sequence of SEQ ID No: 5, but also to equivalents that have the same or similar functions or activities as wild-type SNCG protein, even though their sequence portions are different, and equivalents may include amino acid sequences that have about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more sequence homology with the amino acid sequence of SEQ ID No: 5.

[0037] It is known that VTN (vitin, NCBI gene ID: 7448) protein is a heme-binding protein family glycoprotein synthesized in the liver. It promotes cell adhesion and migration by binding to integrin α-Vβ-3 to connect cells to the extracellular matrix, and participates in hemostasis as a component of platelets.

[0038] In this disclosure, VTN protein refers not only to wild-type VTN protein composed of the amino acid sequence of SEQ ID No: 6, but also to equivalents that have the same or similar functions or activities as wild-type VTN protein, even though their sequence portions are different, and equivalents may include amino acid sequences that have about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more sequence homology with the amino acid sequence of SEQ ID No: 6.

[0039] FBXO4 (F-box protein 4, NCBI gene ID: 26272) is a protein-coding factor characterized by an F-box (an amino acid motif of approximately 40 residues). It is known to directly contribute to cell transformation, tumorigenesis, and progression by producing Fbx proteins that do not contain or recognize motifs capable of incorporating other protein-protein interaction modules. Furthermore, FBXO4 has been reported as a tumor suppressor with tumor-suppressive activity associated with dysregulation of cyclin D1 protein degradation.

[0040] In this disclosure, FBXO4 protein refers not only to the wild-type FBXO4 protein composed of the amino acid sequence of SEQ ID No: 7, but also to equivalents that have the same or similar functions or activities as the wild-type FBXO4 protein, even though their sequence portions are different, and equivalents may include amino acid sequences that have about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more sequence homology with the amino acid sequence of SEQ ID No: 7.

[0041] Synaptotagmin-like 4 (SYTL4, NCBI gene ID: 94121) protein has an N-terminal Rab27 binding domain and a C-terminal tandem C2 domain, and is known to bind to Rab GTPases to participate in intracellular membrane transport, mediate the release of cleaved granules into the cell, and regulate the secretion of pancreatic and pituitary hormones.

[0042] In this disclosure, SYTL4 protein refers not only to the wild-type SYTL4 protein composed of the amino acid sequence of SEQ ID No: 8, but also to equivalents that have the same or similar functions or activities as the wild-type SYTL4 protein, even though their sequence portions are different, and equivalents may include amino acid sequences that have about 70% or more, about 75% or more, about 80% or more, about 85% or more, about 90% or more, about 92% or more, about 95% or more, about 97% or more, about 98% or more, or about 99% or more sequence homology with the amino acid sequence of SEQ ID No: 8.

[0043] The composition for diagnosing radioresistance in colorectal cancer according to this disclosure may include, as an active ingredient, a reagent for measuring the expression level of mRNA or the expression level of protein encoded by two, three, four, five, six, seven, or eight genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4.

[0044] Additionally, the composition for predicting the prognosis of radiotherapy for colorectal cancer according to this disclosure may include, as an active ingredient, a reagent for measuring the expression level of mRNA or the expression level of protein encoded by two, three, four, five, six, seven, or eight genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4.

[0045] In specific embodiments of this disclosure, the mRNA of genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4, or the proteins encoded by these genes, were identified to have different expression levels in radioresistant and sensitive colorectal cancer cells, and were closely associated with reduced survival rates in colorectal cancer patients.

[0046] Therefore, reagents used to measure the expression levels of mRNAs of one or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4, or the expression levels of proteins encoded by one or more of these genes, can more effectively diagnose radioresistance in colorectal cancer and predict the prognosis of radiotherapy for colorectal cancer than mRNAs and / or proteins of other genes and combinations thereof. Consequently, the efficiency and outcomes of radiotherapy for colorectal cancer can be improved by determining whether radiotherapy should be performed and by setting the optimal radiation dose for radiotherapy.

[0047] Specifically, in colorectal cancer cells, the expression of CXCL5, CD68, MATN1, SERPING1, SNCG, and VTN genes was upregulated due to radiation exposure, while the expression of FBXO4 and SYTL4 genes was downregulated.

[0048] More specifically, the expression of CXCL5, CD68, and MATN1 genes was upregulated in radioresistant colorectal cancer cells, while the expression of SERPING1, SNCG, and VTN genes was upregulated in radiosensitive colorectal cancer cells.

[0049] Specifically, the genes CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4 may be genes whose upregulation is associated with reduced survival rates in colorectal cancer patients.

[0050] Therefore, radioresistance can be determined when the expression levels of mRNA of two or more genes in the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, and VTN, or the expression levels of proteins encoded by these two or more genes, are higher than those in the normal control group. Conversely, lower expression levels indicate lower radioresistance or radiosensitivity. For example, high expression of mRNA of two to six genes and / or two to six proteins encoded by these genes in the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, and VTN indicates high radioresistance, while low expression of mRNA of these two to six genes and / or two to six proteins encoded by these genes indicates low radioresistance.

[0051] Furthermore, when the expression levels of the mRNA of the FBXO4 and SYTL4 genes or the expression levels of the proteins encoded by these genes are lower than those of the normal control group, radioresistance can be determined, and when the expression levels are higher, radioresistance or radiosensitivity can be determined.

[0052] Furthermore, when the expression levels of mRNA or proteins encoded by two or more genes in the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, and VTN are higher than those in the normal control group, the prognosis of radiotherapy for colorectal cancer can be determined to be negative; conversely, when the expression levels are lower, the prognosis of radiotherapy for colorectal cancer can be determined to be positive. For example, when the mRNA of two to six genes in the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, and VTN and / or the two to six proteins encoded by those genes are all highly expressed, the prognosis of radiotherapy for colorectal cancer can be determined to be negative; and when the mRNA of two to six genes and / or the two to six proteins encoded by those genes are all low expressed, the prognosis of radiotherapy for colorectal cancer can be determined to be positive.

[0053] Furthermore, when the expression levels of FBXO4 and SYTL4 mRNA or the protein encoded by these genes are lower than those in the normal control group, the prognosis of radiotherapy for colorectal cancer can be determined to be negative, and when the expression levels are higher, the prognosis of radiotherapy for colorectal cancer can be determined to be positive.

[0054] Furthermore, the compositions for diagnosing radioresistance in colorectal cancer and the compositions for predicting the prognosis of radiotherapy for colorectal cancer according to this disclosure may include reagents for measuring the expression level of mRNA of the SERPING1 or SNCG gene, or the expression level of a protein encoded by the gene.

[0055] In this disclosure, the term "radioresistance" refers to a state in which cells are not easily affected by radiation exposure and exhibit less change in repair or proliferation when exposed to radiation. Conversely, the term "radiosensitivity" refers to a state in which cells are easily affected by radiation exposure and exhibit change in repair or proliferation when exposed to radiation.

[0056] In this disclosure, the term "radiotherapy" refers to cancer treatment that induces cancer cell death through a mechanism that causes DNA damage in cancer cells by irradiating them, thereby inhibiting cell division. In the treatment of solid tumors, radiotherapy can be administered for curative, adjuvant, or remission purposes, and can be performed alone, in combination with surgical treatment, or in combination with chemotherapy agents or radiosensitizers.

[0057] In this disclosure, colorectal cancer may include colon cancer and rectal cancer.

[0058] In this disclosure, the term "diagnosis" includes determining a subject's susceptibility to a particular disease or disorder, determining whether a subject currently has a particular disease or disorder, determining the prognosis of a subject with a particular disease or disorder, or performing therapeutic measurements (e.g., monitoring the subject's condition to provide information about the treatment effect).

[0059] In this disclosure, the term "prognosis" refers to the prospect or preliminary assessment of a disease's medical outcome and includes both positive and negative prognoses. Positive prognoses include improvement or stabilization of the disease, such as disease remission, tumor regression, long-term survival potential, or disease-free survival, while negative prognoses include disease progression or lethality, such as decreased survival, recurrence, tumor growth, metastasis, or drug resistance.

[0060] Furthermore, in this disclosure, the term "prediction" refers to medical inference, such as the anticipation of the course of a disease (such as disease progression, improvement, recurrence, tumor growth, drug resistance, probability of death after treatment, or survival rate) or the responsiveness to treatment methods such as chemotherapy or radiotherapy.

[0061] Specifically, in this disclosure, the diagnosis can be a diagnosis of radioresistance in colorectal cancer, and the prognostic prediction can be a prognostic prediction of radiotherapy for colorectal cancer.

[0062] In this disclosure, the measurement of mRNA expression level refers to the process of determining the presence and expression level of mRNA of a gene in a biological sample, used for diagnosing radioresistance in colorectal cancer and / or predicting the prognosis of radiotherapy for colorectal cancer; the reagents used to measure mRNA expression level may include primers, probes or antisense nucleotides that specifically bind to a gene or mRNA, and the measurement of mRNA expression level may be performed by one or more methods selected from the group consisting of RT-PCR, competitive RT-PCR, real-time RT-PCR, RNase protection assay (RPA), Northern blotting and DNA microarray analysis, but this disclosure is not limited thereto.

[0063] In this disclosure, the measurement of protein expression levels refers to the process of determining the presence and degree of expression of proteins in a biological sample for the diagnosis of radioresistance in colorectal cancer and / or the prediction of prognosis in radiotherapy for colorectal cancer. Reagents used to measure protein expression levels may include peptides, compounds, antibodies, or aptamers that can specifically bind to proteins. The measurement of protein expression levels can be performed by one or more methods selected from the group consisting of Western blotting, enzyme-linked immunosorbent assay (ELISA), radioimmunoassay (RIA), radioimmunodiffusion, Ouchterlony immunodiffusion, rocket immunoelectrophoresis, immunohistochemistry, dual-luciferase reporter assay, immunoprecipitation assay, complement fixation assay, fluorescence activated cell sorting (FACS), and protein microarray analysis, but this disclosure is not limited thereto.

[0064] In this disclosure, "sample" can refer to a sample derived from a subject who has received radiotherapy or from whom a decision needs to be made regarding radiotherapy. For example, the term "sample" means a sample capable of determining the expression level of mRNA or protein encoded by two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4, and may include the subject's cells, tissues, whole blood, serum, plasma, saliva, sputum, cerebrospinal fluid, or urine, but this disclosure is not limited thereto. In this disclosure, "subject" refers to an individual to be evaluated for the likelihood of developing radioresistance or colorectal cancer progression, or to predict the prognosis of radiotherapy. There are no specific limitations on the subject, as long as it is an animal that is likely to develop colorectal cancer, but specifically it can be a mammal, such as a human (Homo sapiens).

[0065] In this disclosure, the term "expression level" may be used interchangeably with "expression signature" or "expression profile," and may include the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4, or the expression level of proteins encoded by such two or more genes. Expression level may include an increase or decrease in expression, and expression level may be measured in cancer cells isolated from the subject before and / or after radiotherapy. Simultaneously, expression level can be determined by measuring the amount of mRNA and / or protein of the gene in a sample.

[0066] In this disclosure, the term "primer" refers to a short nucleic acid sequence having a free 3'-hydroxyl end, which can form a base pair with a complementary template and serve as the starting point for replicating the template strand. Under appropriate buffer conditions and temperature, primers can initiate DNA synthesis in the presence of reagents used for polymerization (i.e., DNA polymerase or reverse transcriptase) and four different nucleoside triphosphates. The primers of this disclosure are primers capable of binding complementary to the biomarker gene or mRNA of this disclosure, and can be positive or antisense nucleic acids with nucleotide sequences of 7 to 50 bases, and can incorporate additional features that do not alter the fundamental nature of the primer as the starting point for DNA synthesis. Furthermore, the primers of this disclosure can be chemically synthesized using methods supported by phosphorous amide solids or other well-known methods, and can be modified using various methods known in the art. Non-limiting examples of such modifications include methylation, capping, substitution of analogs containing one or more natural nucleotides, and modifications between nucleotides, such as modifications to uncharged links (e.g., methylphosphonates, triphosphates, aminophosphates, carbamates, etc.) or charged links (e.g., thiophosphates, dithiophosphates, etc.). Nucleic acids may contain one or more additional covalently bound residues, such as proteins (e.g., nucleases, toxins, antibodies, signal peptides, or poly-L-lysine), intercalating agents (e.g., acridine or psoralen), chelating agents (e.g., metals, radioactive metals, iron, or oxidized metals), and alkylating agents. Additionally, the primers of this disclosure may be modified using labels capable of providing a detectable signal directly or indirectly, such as radioisotopes, fluorescent molecules, or biotin.

[0067] In this disclosure, the term "probe" refers to a nucleic acid that can bind complementaryly to mRNA and is produced by an enzymatic or chemical purification or synthesis process, having a length of several to hundreds of bases. The probes of this disclosure are probes capable of binding complementaryly to the biomarker gene or mRNA of this disclosure, and can be labeled with radioisotopes or enzymes to identify the presence or absence of mRNA, and can be designed and modified by known methods.

[0068] In this disclosure, the term "antense nucleotide" refers to DNA, RNA, or a derivative thereof containing a nucleic acid sequence complementary to the sequence of a specific mRNA, and binding to the complementary sequence within the mRNA and inhibiting the translation of the mRNA into a protein. The sequence of the antisense nucleotide refers to a DNA or RNA sequence complementary to the mRNA of the biomarker gene of this disclosure and capable of binding to the mRNA. This can inhibit the essential activity of the mRNA in translation, translocation to the cytoplasm, maturation, or any other overall biological function. Antisense nucleotides can be synthesized in vitro and administered in vivo using conventional methods, or can be produced in vivo, and antisense nucleotides suitable for use in this disclosure can be prepared according to methods known in the art, referring to the nucleotide and / or amino acid sequences of the biomarker genes and / or proteins of this disclosure.

[0069] In this disclosure, the term "antibody" refers to a globulin-type protein that circulates in the blood or lymph within the immune system of a living organism and reacts with invading external substances (i.e., antigens), and specifically binds to an antigen. For the purposes of this disclosure, an antibody refers to an antibody that specifically binds to the biomarker protein of this disclosure, and may include polyclonal antibodies, monoclonal antibodies, and recombinant antibodies, and includes not only the complete form having two full-length light chains and two full-length heavy chains, but also functional fragments of the antibody molecule. A functional fragment of an antibody molecule is a fragment that at least retains antigen-binding function, and examples include Fab, F(ab'), F(ab')2, and Fv. Antibodies that specifically bind to the biomarker protein of this disclosure may be generated by methods known to those skilled in the art, such as by injecting the immunogenic biomarker protein into an external host. External hosts may include mammals such as mice, rats, sheep, and rabbits, and the immunogen may be injected intramuscularly, intraperitoneally, or subcutaneously, and is typically administered with an adjuvant to enhance antigenicity. Subsequently, blood can be collected periodically from external hosts, and serum that shows specificity to the antigen can be obtained, from which antibodies can be isolated.

[0070] In this disclosure, the term "aptamer" is a single-stranded oligonucleotide having a length of about 20 to 60 nucleotides, and refers to a nucleic acid molecule that has binding activity to a specific target molecule. Aptamers have various three-dimensional structures depending on their sequence, exhibit high affinity for specific substances, such as antigen-antibody reactions, and bind to specific target molecules, thereby inhibiting the activity of those target molecules. Aptamers can be RNA, DNA, modified nucleic acids, or mixtures thereof, and can be linear or circular. In this disclosure, aptamers can specifically bind to proteins encoded by biomarker genes of this disclosure and can be prepared by those skilled in the art from the nucleotide sequence of the biomarker genes of this disclosure using known methods.

[0071] 2. Kits for diagnosing radioresistance in colorectal cancer and for predicting radiotherapy for colorectal cancer. After the reagent kit Another aspect of this disclosure provides a kit for diagnosing radioresistance in colorectal cancer.

[0072] Furthermore, another aspect of this disclosure provides a kit for predicting the prognosis of radiotherapy for colorectal cancer.

[0073] The kit for diagnosing radioresistance in colorectal cancer according to this disclosure comprises, as an active ingredient, a reagent for measuring the expression level of mRNA or protein encoded by two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4.

[0074] In addition, the kit for predicting the prognosis of radiotherapy for colorectal cancer according to this disclosure includes, as an active ingredient, a reagent for measuring the expression level of mRNA or the expression level of protein encoded by two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4.

[0075] The descriptions above, which relate to compositions used for diagnosing radioresistance in colorectal cancer or for predicting the prognosis of radiotherapy for colorectal cancer, will be omitted.

[0076] In this disclosure, the term "kit" refers to a tool for diagnosing radioresistance in colorectal cancer or predicting the prognosis of radiotherapy for colorectal cancer by determining the expression levels of mRNA or proteins encoded by two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4. Kits of this disclosure may include reagents for measuring the expression levels of mRNA or proteins encoded by two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4, and specifically may include primers, probes, and antisense nucleotides that specifically bind to the mRNA of a gene, or peptides, compounds, antibodies, and aptamers that specifically bind to a protein, and may also include one or more other compositions, solutions, or devices suitable for the analytical method.

[0077] In addition, the kit may include a user manual describing optimal reaction conditions. The manual may include instructions in the form of a booklet or leaflet, a label attached to the kit, or a description on the surface of the kit packaging, and may also include information disclosed or provided through electronic media such as the Internet.

[0078] In this disclosure, the kit may be an RT-PCR kit, a microarray chip kit, a DNA kit, an ELISA kit, a protein chip kit, or a rapid kit.

[0079] 3. Methods for providing information on radioresistance for diagnosing colorectal cancer and methods for providing information on radioresistance for predicting colorectal cancer. Methods for obtaining prognostic information on injection therapy Another aspect of this disclosure provides a method for providing information on radioresistance for diagnosing colorectal cancer.

[0080] Furthermore, another aspect of this disclosure provides a method for providing information on the prognosis of radiotherapy for colorectal cancer.

[0081] The method for providing information on radioresistance for diagnosing colorectal cancer according to this disclosure includes: (a) measuring the expression level of mRNA or the expression level of protein encoded by two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 in a sample isolated from a subject, and (b) comparing the expression level of the mRNA or protein with the expression level of the mRNA or protein in a normal control group.

[0082] The method according to this disclosure for providing information on the prognosis of radiotherapy for colorectal cancer includes: (a) measuring the expression level of mRNA or the expression level of protein encoded by two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 in a sample isolated from a subject, and (b) comparing the expression level of the mRNA or protein with the expression level of the mRNA or protein in a normal control group.

[0083] The same descriptions as those previously described in "1. Compositions for diagnosing radioresistance of colorectal cancer or predicting the prognosis of radiotherapy for colorectal cancer" are omitted here.

[0084] In the method for providing information on radioresistance for diagnosing colorectal cancer according to the present disclosure, step (a) may include measuring the expression level of mRNA of the SERPING1 or SNCG gene or the expression level of a protein encoded by the gene.

[0085] Furthermore, in the method for providing information on the prognosis of radiotherapy for colorectal cancer according to this disclosure, step (a) may include measuring the expression level of mRNA of the SERPING1 or SNCG gene or the expression level of a protein encoded by the gene.

[0086] In the method for providing information on radioresistance in colorectal cancer according to this disclosure, in step (b), when the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, and VTN, or the expression level of protein encoded by the two or more genes, is compared with the expression level of mRNA or protein in a normal control group, and it is found that the expression level is higher than that in the normal control group, radioresistance in colorectal cancer can be determined. High expression levels may include a subject's expression level being similar to that of a normal control group, or an increase in the subject's expression level by 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, or 1000% or higher compared to the expression level in the normal control group.

[0087] Furthermore, in the method for providing information on radioresistance in colorectal cancer according to this disclosure, in step (b), when the expression levels of the mRNA of the FBXO4 and SYTL4 genes, or the expression levels of the proteins encoded by these genes, are compared with the expression levels of the mRNA or proteins of a normal control group, and it is found that the expression levels are lower than those of the normal control group, radioresistance in colorectal cancer can be determined. Low expression levels may include a subject's expression level being similar to that of a normal control group, or a subject's expression level being reduced by 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 99% or more compared to the expression levels of a normal control group.

[0088] In the method for providing information predicting the prognosis of radiotherapy for colorectal cancer according to this disclosure, in step (b), when the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, and VTN, or the expression level of proteins encoded by these two or more genes, is compared with the expression level of mRNA or protein in a normal control group, and it is found that the expression level is higher than that in the normal control group, the prognosis of radiotherapy for colorectal cancer can be determined to be negative. High expression levels may include a subject's expression level being similar to that of a normal control group, or an increase in the subject's expression level by 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, 200%, 300%, 400%, 500%, 600%, 700%, 800%, 900%, or 1000% or higher compared to the expression level in the normal control group.

[0089] Furthermore, in the method for providing information predicting the prognosis of radiotherapy for colorectal cancer according to this disclosure, in step (b), when the expression levels of the mRNA of the FBXO4 gene and the SYTL4 gene, or the expression levels of the proteins encoded by these genes, are compared with the expression levels of the mRNA or proteins of a normal control group, and it is found that the expression levels are lower than those of the normal control group, the prognosis of radiotherapy for colorectal cancer can be determined to be negative. Low expression levels may include a subject's expression level being similar to that of a normal control group, or a subject's expression level being reduced by 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 99% or more compared to the expression levels of a normal control group.

[0090] Furthermore, in the method for providing information on radioresistance in colorectal cancer according to this disclosure, the method may further include: (c-1) determining that the colorectal cancer is radioresistant when the expression level of the mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG and VTN, or the expression level of the protein encoded by the two or more genes, is higher than the expression level of the normal control group; and / or, (c-2) determining that the colorectal cancer is radioresistant when the expression level of the mRNA of the FBXO4 gene and the SYTL4 gene, or the expression level of the protein encoded by the gene, is lower than the expression level of the normal control group.

[0091] Furthermore, in the method for providing information on the prognosis of radiotherapy for colorectal cancer according to this disclosure, the method may further include: (c-1) determining that the prognosis of radiotherapy for colorectal cancer is negative when the mRNA expression level of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG and VTN or the expression level of the protein encoded by the two or more genes is higher than the expression level of the normal control group; and / or, (c-2) determining that the prognosis of radiotherapy for colorectal cancer is negative when the mRNA expression level of the FBXO4 gene and the SYTL4 gene or the expression level of the protein encoded by the gene is lower than the expression level of the normal control group.

[0092] In a specific embodiment of this disclosure, genes or combinations thereof with a p-value of 0.05 or less are identified by analyzing overall survival (OS) using TCGA data, and a hazard ratio (HR) value is determined for each identified gene or combination. HR represents risk, and a higher HR value in the high-expression group indicates a lower survival rate for the subject. When the HR is 1.5 or higher, 1.6 or higher, 1.7 or higher, 1.8 or higher, 1.9 or higher, or 2.0 or higher, the prognosis for radiotherapy to colorectal cancer in the subject can be determined to be negative.

[0093] Another aspect of this disclosure provides a method for diagnosing radioresistance in colorectal cancer, comprising: (a) measuring the expression level of mRNA or protein encoded by two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 in a sample isolated from a subject; and (b) comparing the expression level of the mRNA or protein with the expression level of the mRNA or protein in a normal control group.

[0094] Another aspect of this disclosure provides a method for predicting the prognosis of radiotherapy for colorectal cancer, comprising: (a) measuring the expression level of mRNA or protein encoded by two or more genes selected from a group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 in a sample isolated from a subject; and (b) comparing the expression level of the mRNA or protein with the expression level of the mRNA or protein in a normal control group. Another aspect of this disclosure provides the use of reagents for measuring the expression levels of mRNAs of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4, or the expression levels of proteins encoded by said two or more genes, for the diagnosis of radioresistance in colorectal cancer.

[0095] Another aspect of this disclosure provides the use of reagents for measuring the expression levels of mRNAs or proteins encoded by two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4 for predicting the prognosis of radiotherapy for colorectal cancer.

[0096] Beneficial effects In this disclosure, the mRNA of the genes CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4, or the proteins encoded by these genes, exhibit different expression levels in radioresistant and radiosensitive colorectal cancer cells, and are closely associated with reduced survival rates in colorectal cancer patients. Therefore, reagents for measuring the expression levels of the mRNA of genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4, or the expression levels of the proteins encoded by these genes, can effectively diagnose radioresistance in colorectal cancer or predict the prognosis of radiotherapy for colorectal cancer. This, in turn, can improve the efficiency and outcomes of radiotherapy for colorectal cancer by determining whether radiotherapy should be administered and by setting the optimal radiation dose for radiotherapy.

[0097] However, the effects of this disclosure are not limited to those described above, and those skilled in the art will clearly understand from the following description other effects not mentioned. Attached Figure Description

[0098] Figure 1 The results of measuring the radiosensitivity of human colorectal cancer cell lines HT29 and HCT116 are shown.

[0099] Figure 2 The results show the analysis of genes whose expression levels increased or decreased after irradiation with an 8 Gy dose in human colorectal cancer cell lines HT29 and HCT116.

[0100] Figure 3 The results show the analysis of changes in the expression of proteins of radiation-responsive genes in human colorectal cancer cell lines HT29 and HCT116.

[0101] Figure 4 The results show the analysis of expression levels and risks of CXCL5 and CD68 genes using DESeq2 based on RNA-seq data (GSE107422) from 110 patients who experienced recurrence after colorectal cancer onset.

[0102] Figure 5a Kaplan-Meier survival curves are shown for colorectal cancer patients based on the expression levels of VTN, SNCG, or SERPING1.

[0103] Figure 5b Kaplan-Meier survival curves are shown for colorectal cancer patients based on the expression levels of VTN and MATN1, VTN and SERPING1, SNCG and SYTL4, SNCG and CD68, or SNCG and FBXO4.

[0104] Figure 6a The changes in cell viability measured after knocking out the expression of the radioresistance gene via siRNA in the human colorectal cancer cell line HCT116 are shown.

[0105] Figure 6b The changes in cell viability measured in the human colorectal cancer cell line HT29 after knocking out the expression of the radioresistance gene via siRNA are shown. Detailed Implementation

[0106] The present disclosure will now be described in detail with reference to the embodiments.

[0107] However, the following embodiments are provided to illustrate this disclosure, and the scope of this disclosure is not limited to the following embodiments.

[0108] Example 1. Measurement of radiosensitivity of colorectal cancer cell lines Human colorectal cancer cell lines HT29 and HCT116 were purchased from ATCC (American Type Culture Collection, USA) and maintained in RPMI-1640 medium supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin (10000 U / ml) at 37°C and 5% CO2. Subsequently, to measure the radiosensitivity of colorectal cancer cells, each cell line was seeded at an appropriate number in 60 mm culture dishes, and after 24 hours, the cells were exposed to an appropriate dose of radiation and then cultured at 37°C and 5% CO2 for 10 to 14 days. Afterward, the formed cell colonies were washed with phosphate-buffered saline (PBS) and stained with a mixture of 1% methylene blue and 100% methanol. The stained cell colonies (colonies containing 50 or more cells) were air-dried at room temperature and visually counted in each culture dish.

[0109] The results showed that, after radiation exposure, the survival rate of the HT29 cell line was significantly higher than that of the HCT116 cell line, and the radioresistance of the HT29 cell line was also identified as higher than that of the HCT116 cell line. Figure 1 ).

[0110] Example 2. Development of radioresponsive genes in colorectal cancer To develop radioresponsive genes in colorectal cancer, genes were selected based on transcriptomic data analyzed from HT29 and HCT116 cell lines, and the radioresponsiveness of each gene was measured by real-time reverse transcription polymerase chain reaction (real-time RT-PCR). Primer information used in this embodiment is shown in Table 1 below.

[0111] [Table 1]

[0112] Subsequently, HT29 and HCT116 cell lines were exposed to 0 or 8 Gy of radiation, and the expression of each gene was measured after exposure. The results showed that radiation exposure increased the expression of CXCL5, CD68, MATN1, SERPING1, SNCG, and VTN in both cell lines, while radiation exposure decreased the expression of FBXO4 and SYTL4 in both cell lines. Figure 2 Furthermore, it was shown that CXCL5, CD68, and MATN1 were highly expressed in the HT29 cell line, which exhibited relatively high radioresistance, while SERPING1, SNCG, and VTN were highly expressed in the HCT116 cell line, which exhibited relatively high radiosensitivity. FBXO4 and SYTL4 showed similar expression levels in both cell lines.

[0113] Example 3. Identification of changes in protein expression in radioresponsive factors To identify the protein expression patterns of the radiation-responsive genes derived from Example 2 after radiation exposure, Western blot analysis was performed by extracting proteins from HT29 and HCT116 cell lines 24 hours after irradiation with an 8 Gy dose. Information on the antibodies used in this example is shown in Table 2 below.

[0114] [Table 2]

[0115] As a result, CXCL5 was highly expressed in the HT29 cell line, which exhibited relatively high radioresistance, while SNCG was highly expressed in the HCT116 cell line, which exhibited relatively high radiosensitivity. Furthermore, radiation exposure significantly increased VTN protein levels, while FBXO4 protein levels decreased. Figure 3 Meanwhile, CD68, CXCL5, SNCG, and SERPING1 are all secreted proteins and are known to be closely associated with the activation of immune cells around tumors, and the reduction observed in the protein blot may indicate an increase in secretion into the culture medium.

[0116] Example 4. Analysis of risk and survival curves based on the expression of radioresponsive genomes in colorectal cancer patients. To identify the expression patterns of the radioactive genes derived from Example 2 in actual colorectal cancer patients, data from 110 patients (GSE107422) who experienced recurrence after colorectal cancer onset were downloaded and analyzed using the DESeq2 program. The results showed that the expression of CXCL5 and CD68 was significantly increased by 3.946-fold and 1.46-fold, respectively, as shown in Table 3 below.

[0117] [Table 3]

[0118] Furthermore, analysis of overall survival in cancer patients based on CXCL5 and CD68 expression showed that higher CXCL5 expression significantly reduced overall survival with a risk of 1.51, and higher CD68 expression also significantly reduced overall survival with a risk increasing to 2.01. Figure 4 ).

[0119] Subsequently, to analyze the impact of radioresponsive gene expression from Example 2 on the survival of colorectal cancer patients, overall survival (OS) was analyzed using Cancer Genome Atlas (TCGA) data via GEPIA2, and genes or combinations showing a p-value of 0.05 or lower were identified. The results are shown in Table 4 below. In Table 4, the hazard ratio (HR) represents the risk level, and a higher HR value in the group with high gene expression indicates poorer patient survival. Furthermore, based on the expression of the aforementioned genes or gene combinations, the survival of colorectal cancer patients was analyzed and visualized using Kaplan-Meier survival curves. Figure 5a and Figure 5b ).

[0120] [Table 4]

[0121] The analysis showed that the risk associated with increased SNCG expression and colorectal cancer patient survival was 1.7, as was the risk associated with increased SERPING1 expression. This indicates that increased SNCG and SERPING1 expression alone determined an increased risk and decreased survival, and they can be classified as radioresistance factors. Furthermore, regarding SNCG, the risk was further increased when it was co-expressed with CD68, SYTL4, or FBXO4. Simultaneously, the risk associated with increased VTN expression alone was 1.4, which was statistically insignificant, while the co-increase in VTN / MATN1 or VTN / SERPING1 expression showed a significant decrease in overall survival, with risks of 1.5 and 1.7, respectively.

[0122] Because increased expression of FBXO4 and SYTL4, along with other genomic genes, is associated with shortened overall survival in colorectal cancer patients, and because the expression of FBXO4 and SYTL4 decreases with radiation exposure, colorectal cancer patients with high expression of FBXO4 and SYTL4 are suitable candidates for radiotherapy and may have a positive prognosis with radiotherapy. Since increased expression of these genes is directly associated with decreased survival in colorectal cancer patients, and the expression of CD68, CXCL5, MATN1, SERPING1, SNCG, and VTN increases with radiation exposure, these genes are considered radioresistant, and colorectal cancer patients with high expression of these genes are candidates for exclusion from radiotherapy and may have a negative prognosis with radiotherapy.

[0123] Example 5. Analysis of cell survival after knockout of radioresponsive genes in human colorectal cancer cells. To identify changes in the survival rate of colorectal cancer cells when the expression of the radioresistance gene from Example 2 above was knocked out, changes in the survival rate of colorectal cancer cell lines HT29 and HCT116 were measured after the radioresistance gene expression was knocked out using siRNA.

[0124] Specifically, in 96-well plates, each siRNA was transfected into a colorectal cancer cell line using Lipofectamine™ RNAiMAX transfection reagent (Thermo Fisher Scientific, USA), followed by radiation exposure at a dose of 8 Gy. After 48 hours, cell viability was measured by treating the cells with CCK-8 reagent (DOJINDO, Japan). Information on the siRNAs used in this example is shown in Table 5 below.

[0125] [Table 5]

[0126] As a result, compared with the control group treated with nonspecific RNA (scRNA), a significant decrease in cell viability was observed in the HCT116 cell line when each gene was knocked out, specifically through single-gene knockout of CD68, SERPING1, and VTN, with SERPING1 showing the greatest effect. Furthermore, it was shown that in the HCT116 cell line, cell death was increased by combining gene knockouts such as SNCG / SYTL4, SNCG / CD68, and SNCG / CD68 / VTN compared with single-gene knockout of SNCG. Figure 6a Meanwhile, in the HT29 cell line, no genes were found to induce significant cell death through single-gene knockout. However, compared with the control group, significant cell death effects were observed by combining knockouts of SNCG / SYTL4, SNCG / CD68, and SNCG / CD68 / VTN. Furthermore, compared with single-gene knockout of SNCG, combined knockout of SNCG / CD68 / VTN further increased cell death. Figure 6b ).

[0127] The above experiments demonstrated that measuring the expression of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4 can effectively predict radioresistance to radiotherapy and the prognosis of radiotherapy. Therefore, it is anticipated that when the activity of the above-mentioned radioresistance genomes is determined in conjunction with radiotherapy, cancer treatment may be more effective.

[0128] Representative embodiments of the present disclosure have been described above by way of example, but the scope of the present disclosure is not limited to the specific embodiments described above, and those skilled in the art will be able to make appropriate modifications within the scope set forth in the claims of the present disclosure.

Claims

1. A radioresistant composition for diagnosing colorectal cancer, said composition comprising: A reagent for measuring the expression level of mRNA or protein encoded by two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4 genes.

2. The composition according to claim 1, wherein, The composition includes reagents for measuring the expression level of mRNA of the SERPING1, CD68, or SNCG gene, or the expression level of protein encoded by said gene.

3. The composition according to claim 1, wherein, The reagent used to measure the expression level of the mRNA of the gene is one or more selected from the group consisting of primers, probes and antisense nucleotides that specifically bind to the mRNA of the gene.

4. The composition according to claim 1, wherein, The reagent used to measure the expression level of the protein is one or more selected from the group consisting of peptides, compounds, antibodies, and aptamers that specifically bind to the protein.

5. A kit for diagnosing radioresistance in colorectal cancer, the kit comprising: The composition according to any one of claims 1 to 4.

6. The kit according to claim 5, wherein, The kit is an RT-PCR kit, microarray chip kit, DNA kit, ELISA kit, protein chip kit, or rapid kit.

7. A method for providing information on radioresistance for diagnosing colorectal cancer, the method comprising: (a) Measuring the expression levels of mRNAs of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4, or the expression levels of proteins encoded by two or more of said genes, isolated from samples taken from the subject; and (b) The expression levels of the mRNA or the protein are compared with the expression levels of the mRNA or the protein in the normal control group.

8. The method according to claim 7, wherein, (a) This includes measuring the expression level of mRNA of the SERPING1, CD68, or SNCG gene, or the expression level of protein encoded by said gene.

9. A composition for predicting the prognosis of radiotherapy for colorectal cancer, said composition comprising: A reagent for measuring the expression level of mRNA of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4 and SYTL4, or the expression level of proteins encoded by two or more of said genes.

10. The composition according to claim 9, wherein, The composition includes reagents for measuring the expression level of mRNA of the SERPING1, CD68, or SNCG gene, or the expression level of protein encoded by said gene.

11. The composition according to claim 9, wherein, The reagent used to measure the expression level of the mRNA of the gene is one or more selected from the group consisting of primers, probes, and antisense nucleotides that specifically bind to the mRNA of the gene.

12. The composition according to claim 9, wherein, The reagent used to measure the expression level of the protein is one or more selected from the group consisting of antibodies and aptamers that specifically bind to the protein.

13. A kit for predicting the prognosis of radiotherapy for colorectal cancer, the kit comprising: The composition according to any one of claims 9 to 12.

14. The kit according to claim 13, wherein, The kit is an RT-PCR kit, microarray chip kit, DNA kit, ELISA kit, protein chip kit, or rapid kit.

15. A method for providing information on the prognosis of radiotherapy for colorectal cancer, the method comprising: (a) Measuring the expression levels of mRNAs of two or more genes selected from the group consisting of CXCL5, CD68, MATN1, SERPING1, SNCG, VTN, FBXO4, and SYTL4, or the expression levels of proteins encoded by two or more of said genes, isolated from samples taken from the subject; and (b) The expression levels of the mRNA or the protein are compared with the expression levels of the mRNA or the protein in the normal control group.

16. The method according to claim 15, wherein, (a) This includes measuring the expression level of mRNA of the SERPING1, CD68, or SNCG gene, or the expression level of protein encoded by said gene.

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