From Multi-omics To Colorectal Cancer Biomarkers And Targets

Abstract

Colorectal cancer (CRC) ranks as the second leading cause of cancer-related deaths globally. CRC is primarily caused by germline and/or somatic mutations in colon and rectal epithelial tissues, arising from instability in chromosomes or defects in the DNA mismatch repair machinery. Although early-stage tumors could be removed via surgery with or without other interventions, CRC can still recure, raising the chances of treatment failure. As such, it is extremely important to gain a better understanding of the underlying mechanisms of CRC for the prediction of improved biomarkers and novel therapeutic treatments. In this study, we performed a meta-analysis of publicly available CRC datasets on CDIAM, a multi-omics analytical software platform that offers custom tools to unveil meaningful cell-cell interactions and ligand-receptor pairs (CellphoneDB), identify important pathways (hypergeometric analysis), predict therapeutic targets (Pathway2Targets), and prioritize biomarkers (Biomarker2Validate). The results from this study included several differentially expressed genes/proteins (DEGs) and enriched pathways that consistently appeared across different datasets and -omics data types. From the up-regulated DEGs, our Pathway2Targets tool identified CES2 and PPARD as potential targets for CRC, in which CES2 is responsible for the activation of CPT-11, a current treatment for metastatic CRC. Likewise, we found VEGFA to be the top-ranking transcriptional biomarker for CRC. We also observed a significant upregulation of immune cell interactions with other cell types in CRC patients, particularly macrophages, T cells, and myofibroblasts. Our findings agree with previous CRC studies, confirming the reliability of our computational workflow and analytical pipelines to accurately identify pathways and biomarkers with high clinical- and pathological relevance.

Keywords

Colorectal cancer, CRC, multiomics, multi omics analysis software, CDIAM multi omics studio, colorectal cancer review, colorectal cancer biomarkers and targets