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Discovery and Validation of Serum Biomarkers and Neoantigens for Differentiating Colorectal Cancer from Inflammatory Bowel Diseases

ABSTRACT: Early detection of colorectal cancer (CRC) and distinguishing inflammatory bowel diseases from cancerous conditions significantly improve survival rates. While colonoscopy is the gold standard for CRC detection, it is invasive and associated with potential complications. Therefore, there is a need for blood biomarkers that possess high sensitivity and specificity which can be used for pre-diagnosis. In this study, we screened for serum biomarkers specifically altered in colonoscopy-positive (CP) patients (cancer group) when compared to colonoscopy-negative (CN) patients (suffering from other bowel-related illnesses with symptoms similar to CRC), and healthy control (HC) individuals (n=20 each). Using Data-Independent Acquisition-Mass spectrometry (DIA-MS) analysis, we identified potential protein markers and neoantigens uniquely altered in the CP group compared to the CN group. These biomarkers were validated using a targeted approach, Parallel Reaction Monitoring-Mass Spectrometry (PRM-MS). An independent set of samples (n=10 each) was taken for all the groups.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Colorectal Cancer

SUBMITTER: Keshava Prasad T. S.

LAB HEAD: Dr. T S Keshava Prasad

PROVIDER: PXD065161 | Pride | 2025-06-23

REPOSITORIES: Pride

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Project description:In colorectal cancer (CRC), chromosomal instability (CIN) is typically studied using comparative-genomic hybridization (CGH) arrays. We studied paired (tumor and surrounding healthy) fresh-frozen tissue from 86 CRC patients using Illumina’s Infinium-based SNP array. This method allowed us to study CIN in CRC, with simultaneous analysis of copy number (CN) and B-allele frequency (BAF), which is a representation of allelic composition. This data helped us to detect mono-allelic and bi-allelic amplifications/deletion, copy neutral loss of heterozygosity, and levels of mosaicism for mixed cell populations, some of which can not be assessed with other methods that do not measure BAF. We identified associations between CN abnormalities and different CRC phenotypes (MSI, histological diagnosis, location, tumor grade, stage, MSI and presence of lymph node metastasis). We showed commonalities between regions of CN change observed in CRC and the regions reported in previous studies of other solid cancers (e.g., amplifications of 20q, 13q, 8q, 5p and deletions of 18q, 17p and 8p). From the Therapeutic Target Database we found relevant drugs, targeted to the genes located in these regions with CN changes, approved or in trials for other cancers and common diseases. These drugs may be considered for future therapeutic trials in CRC, based on personalized cytogenetic diagnosis. We also found many regions harboring genes which are not currently targeted by any relevant drugs that may be considered for future drug discovery studies. Our study shows the application of high-density SNP arrays for cytogenetic study in CRC and its importance for personalized treatment. DNA was extracted from colon tissue samples provided by 86 CRC patients. Each patient provided paired CRC tumor tissue and adjacent normal colon mucosa samples, which were fresh-frozen after resection. Samples were genotyped using Illumina's Infinium-based 610 Quad and CytoSNP 12 microarray chips. The genotype data from paired tumor and normal samples was used to detect tumor-specific chromosomal instabilities in copy number, including copy-neutral LOH, which cannot be assessed by many other cytogenetic methods. Supplementary file "GSE34678_raw_GPL8887.txt" includes the raw data for Samples using GPL8887 (GSM853162-GSM853239); supplementary file "GSE34678_raw_GPL13829.txt" includes the raw data for Samples using GPL13829 (GSM853240-GSM853363).

			Action	DRS
	Blank_01-CC.raw	Raw
	CC_CRC_Std10_R1.raw	Raw
	CC_CRC_Std10_R2.raw	Raw
	CC_CRC_Std10_R3.raw	Raw
	CC_CRC_Std11_R1.raw	Raw

Dataset Information

Discovery and Validation of Serum Biomarkers and Neoantigens for Differentiating Colorectal Cancer from Inflammatory Bowel Diseases

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