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Biomarkers for detecting colorectal cancer or adenoma and methods thereof

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

Active Publication Date: 2021-11-26
中精普康(北京)医药科技有限公司
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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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  • Biomarkers for detecting colorectal cancer or adenoma and methods thereof
  • Biomarkers for detecting colorectal cancer or adenoma and methods thereof
  • Biomarkers for detecting colorectal cancer or adenoma and methods thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0175] Example 1 Semi-quantitative untargeted metabolomic analysis in serum from the discovery cohort reveals significantly altered metabolites in CRC and adenoma patients

[0176] The relationship between the serum metabolome and colorectal adenoma or colorectal cancer was determined by untargeted metabolome profiling of the discovery panel by LCMS. Figure 1A is a schematic diagram showing an overview of the experimental design and analysis procedures according to some embodiments of the present application. Such as 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 analysis plot of the distribution of R2 values ​​for non-targeted LC-MS features in negative ion mode and positive ion mode. The R2 values ​​of the linear regression model between the expected and measured mixing ratios for each metabolite detected in the negative and positive ion modes are...

Embodiment 2

[0180] Example 2 Determination of significantly altered gut microbiome-associated serum metabolites in patients with colorectal abnormalities

[0181] Figure 2A is the analysis plot of the program integrating the analysis of fecal metagenome and serum metabolome in the matched group. In total, data from 44 subjects (11 normal and 33 with 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, elevated enterotoxigenic Bacteroides fragilis (ETBF), considered a key pathogen for CRC initiation, was observed. Such as Figure 2C is a plot of the relative abundance of several CRC-associated gut microbiome species in matched cohorts of patients with normal and colorectal abnormalities. Such as Figure 2C As shown, the abundance of several other CRC-promoting species, including Fusobacterium...

Embodiment 3

[0183] Example 3 Prediction of colorectal abnormalities in the discovery cohort based on a list of gut microbiome-associated serum metabolites

[0184] Based on these gut microbiome-associated serum metabolites above, the 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 signatures were significantly altered between normal and CRC or adenoma samples (adjusted p < 5E-3) and were significantly associated with the gut microbiome (p < 1E-3, FDR ≤ 18%). Using group voting, more than 75% of the 200 LASSO runs involved 32 metabolite signatures. Their chemical structure annotations, including MS2 transitions if identifiable, were established by MS / MS spectrum matching as previously described. As mentioned above, Table 1 lists 8 metabolite signatures out of...

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Abstract

A group of diagnostic biomarkers usable for diagnosis of colorectal cancer or colorectal adenoma. A method for detecting colorectal cancer or colorectal adenoma using the group of diagnostic biomarkers is also provided. For example, the method is a non-invasive approach that may utilize serum samples for detecting colorectal cancer. Moreover, the method for detecting colorectal cancer may detect colorectal cancer of different stages (e.g., pre-cancer stage, early stage, middle stage, late stage).

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 954,483, filed December 28, 2019, the entire contents of which are incorporated herein by reference. technical field [0003] The present application mainly relates to the detection of colorectal abnormalities, and in particular to biomarkers and methods for detecting colorectal cancer or adenoma. Background technique [0004] Colorectal cancer (CRC) generally refers to cancer that develops in the colon or rectum (the part of the large intestine). CRC has become an increasingly serious clinical challenge worldwide, and early diagnosis is considered to be an effective way to improve the survival rate of CRC patients. Adenoma usually refers to a benign tumor of epithelial tissue. Colonic adenomas, also called "colorectal adenomas (CRA)" or "adenomatous polyps," tend to become malignant and lead to CRC. Therefore, the diagnosis of CRA or CRC...

Claims

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Application Information

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IPC IPC(8): G01N33/574
CPCG01N30/02G16H20/40G16H10/40G16H20/10G01N2560/00G01N33/57419Y02A90/10G01N2800/56G01N33/6842G01N33/6848G01N33/92
Inventor 林凯戴旭东田宇王冠
Owner 中精普康(北京)医药科技有限公司
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