INTEGRATED TRANSCRIPTOMIC AND EPIGENOMIC ANALYSIS IDENTIFIES PATHWAY-SPECIFIC REGULATORY SIGNATURES IN PRIMARY COLORECTAL CANCER

Abstract

Colorectal cancer (CRC) is among the major causes of mortality due to cancer across the globe. The objective of the proposed study is to examine the molecular changes in colorectal cancer by comparing gene expression and DNA methylation in the critical cancer-related pathways. Gene expression and methylation data in normal and primary and metastatic liver CRC samples were analysed extensively using publicly available data on the Gene Expression Omnibus (GEO). BRB-Array tools and CHAMP package were used in analyzing the differential gene expression and the analysis of methylation. Pearson correlation analysis was used to determine the significant correlations between the expression of the genes and the DNA methylation at different stages of the CRC. It was found out that the genes, which are related to significant cancer-related signaling pathways, such as cell cycle, Notch, p53, PI3K-AKT-mTOR, and Ras-Raf-MEK, have a substantial differentiation in their expression and methylation state. RHEB, DAB2, E2F6, and CTBP2 were the key genes that showed strong positive and negative relationships between methylation and expression, which implies that these are the genes that can contribute to the progression of CRC. Furthermore, the comparison revealed a variety of stage-specific epigenetic and transcriptional changes, and the specific molecular phenotypes were found in primary and metastatic CRC. Combination of gene expression and methylation data offers more insight into the regulation mechanisms of CRC, and this may be used as biomarkers of early detection and therapeutic targets. These genes should be experimentally vindicated in future to boost the confidence of the findings and clinical utilisation.