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Biomarker for detecting colorectal cancer or adenoma and method thereof

A technology for colorectal cancer and rectal adenoma, applied in the field of colorectal anomaly detection, can solve problems such as low accuracy

Pending Publication Date: 2022-07-29
IBRAINBABY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, many traditional non-invasive methods are less accurate

Method used

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  • Biomarker for detecting colorectal cancer or adenoma and method thereof
  • Biomarker for detecting colorectal cancer or adenoma and method thereof
  • Biomarker for detecting colorectal cancer or adenoma and method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0170] Example 1 Semi-quantitative non-targeted metabolomic analysis in serum from discovery cohort reveals markedly altered metabolites in CRC and adenoma patients

[0171] Associations between serum metabolomes and colorectal adenomas or colorectal cancers were determined by untargeted metabolome profiling of the discovery group by LCMS. Figure 1A is a schematic diagram of an overview of the experimental design and analysis procedures shown in accordance with some embodiments of the present application. like Figure 1A As shown, the discovery group was divided into normal group, adenoma group, and colorectal cancer group. Low abundance signals (eg, mean abundance Figure 1B is an analytical graph of the distribution of R2 values ​​for non-targeted LC-MS features in negative and positive ion mode. The R2 values ​​of the linear regression model between the expected and measured mixing ratios for each metabolite detected in negative and positive ion modes are shown in Figu...

Embodiment 2

[0175] Example 2 Determination of significantly altered gut microbiome-related serum metabolites in patients with colorectal abnormalities

[0176] Figure 2A is an analysis map of the program for the integrated analysis of the fecal metagenome and serum metabolome in the matched set. In total, data from 44 subjects (11 normal and 33 colorectal abnormalities) passed quality control. Taxonomic analysis of metagenomic data revealed 12,455 microbiome species. Figure 2B is a bar graph of the 15 OUTs in each individual at the species level. Among the top 15 most abundant species, an increase was observed in enterotoxigenic Bacteroides fragilis (ETBF), which is considered a key pathogen for CRC initiation. like Figure 2C is an analysis of the relative abundance of several CRC-associated gut microbiome species in matched cohorts of normal and colorectal abnormal patients. like Figure 2C showed that the abundance of several other CRC-promoting species, including Fusobacterium...

Embodiment 3

[0178] Example 3 Prediction of colorectal abnormalities in the discovery group based on a list of gut microbiome-associated serum metabolites

[0179] Based on these gut microbiome-related serum metabolites, a LASSO algorithm was performed to find key metabolite biomarkers of colorectal abnormalities. The LASSO algorithm with 10-fold cross-validation (CV) was used for feature selection from previously determined serum metabolomic data and gut microbiome metabolomic data. 322 metabolite profiles were significantly altered between normal and CRC or adenoma samples (adjusted p<5E-3) and significantly associated with gut microbiome (p<1E-3, FDR≤18%). Using panel voting, more than 75% of the 200 LASSO runs involved 32 metabolite signatures. Annotations of their chemical structures, including MS2 transitions (if identifiable) were established by MS / MS spectral matching as previously described. As mentioned above, Table 1 lists 8 metabolite signatures out of 32 metabolite signature...

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Abstract

The present disclosure provides a set of diagnostic biomarkers useful for diagnosing colorectal cancer or colorectal adenoma, and also provides a method for detecting colorectal cancer or colorectal adenoma using the diagnostic biomarker set. For example, the method provided by the present disclosure is a non-invasive method that can detect colorectal cancer using a serum sample. In addition, the method for detecting colorectal cancer can detect colorectal cancer in different stages (e.g., pre-cancerous, early, mid-term, and advanced stages).

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application is a divisional application of the Chinese Patent Application No. 202080030060.1 filed on December 28, 2020, and the parent application requires the priority of the US Provisional Patent Application No. 62 / 954,483 filed on December 28, 2019 rights, the entire contents of which are incorporated herein by reference. technical field [0003] The present application generally relates to the detection of colorectal abnormalities, in particular to biomarkers and methods for the detection of colorectal cancer or adenoma. Background technique [0004] Colorectal cancer (CRC) generally refers to cancer that develops from the colon or rectum (part of the large intestine). CRC has become an increasingly serious clinical challenge worldwide, and early diagnosis is considered an effective method to improve the survival rate of CRC patients. Adenomas usually refer to benign tumors of epithelial tissue. Colon adeno...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6869C12Q1/6886G01N30/02G16H10/40G16H20/10G16H20/40G16H50/50
CPCG01N30/02G16H20/40G16H10/40G16H20/10G01N2560/00G01N33/57419Y02A90/10G01N2800/56G01N33/6842G01N33/6848G01N33/92
Inventor 林凯戴旭东田宇
Owner IBRAINBABY
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