A comprehensive multi-omics study reveals potential prognostic and diagnostic biomarkers for colorectal cancer

Abstract

ABSTRACTBackgroundColorectal cancer (CRC) is a complex disease with diverse genetic alterations and causes 10% of cancer-related deaths worldwide. Understanding its molecular mechanisms is essential for identifying potential biomarkers and therapeutic targets for its effective management.MethodWe integrated copy number alterations (CNA) and mutation data via their differentially expressed genes termed as candidate genes (CGs) computed using bioinformatics approaches. Then, using the CGs, we perform Weighted correlation network analysis (WGCNA) and utilise several hazard models such as Univariate Cox, Least Absolute Shrinkage and Selection Operator (LASSO) Cox and multivariate Cox to identify the key genes involved in CRC progression. We used different machine-learning models to demonstrate the discriminative power of selected hub genes among normal and CRC (early and late-stage) samples.ResultsThe integration of CNA with mRNA expression identified over 3000 CGs, including CRC-specific driver genes likeMYCandAPC. In addition, pathway analysis revealed that the CGs are mainly enriched in endocytosis, cell cycle, wnt signalling and mTOR signalling pathways. Hazard models identified four key genes,CASP2, HCN4, LRRC69andSRD5A1, that were significantly associated with CRC progression and predicted the 1-year, 3-years, and 5-years survival times. WGCNA identified seven hub genes:DSCC1, ETV4, KIAA1549, NOP56, RRS1, TEAD4andANKRD13B, which exhibited strong predictive performance in distinguishing normal from CRC (early and late-stage) samples.ConclusionsIntegrating regulatory information with gene expression improved early versus latestage prediction. The identified potential prognostic and diagnostic biomarkers in this study may guide us in developing effective therapeutic strategies for CRC management.