Transcriptomic and targeted genomic profiling of colorectal cancer tissues: an integrative approach.

Efforts are being made in colorectal cancer (CRC) research to improve both diagnosis and treatment choice. In this respect, the high heterogeneity of CRCs, at inter- and intratumoral level, constitutes the main obstacle. Over the last 10 years, the development of new technologies, like next-generation sequencing, have enabled the development of multi-omic profiling of tumors, leading to a better knowledge of CRC biology. CRC classification has achieved significant improvements with the introduction of the consensus molecular subtype classification, an original approach for CRC subtyping based on gene expression. Here, we propose a strategy that integrates transcriptomic, and pan-cancer targeted genomic data for a comprehensive study of CRC in a set of colon and rectal tumor tissues and adjacent mucosa. Tissue specimens collected from 110 CRC patients (tumor and adjacent normal mucosa) were analyzed using RNA-sequencing, small RNA-sequencing, and a 523-gene NGS cancer panel. Eleven tumor samples were classified as MSI high, since they showed more than 20% of MSI sites detected as unstable. APC gene harbored the highest number of unique coding variants detected. 3,849 genes were differentially expressed including, interestingly, several members of the matrix metallopeptidase family upregulated in both comparisons for stage and tumor localization. Several miRNAs were dysregulated and were inversely related to their validated target genes. This study provides more evidence on the importance of an efficient characterization of CRC based on the integration of multi-omics molecular features, and at the same time opens to new opportunities in the identification of non-invasive biomarkers.