Microsatellite Instability of Colon adenocarcinomas in India comprises multiple molecular subtypes

Abstract

The microsatellite stable (MSS) category accounts for more than four-fifths of colon and rectal cancer (CRC). However, studies during the last two decades in the Indian population have shown that the microsatellite instable (MSI) is more than 30% of CRC cases. We have conducted a study to explore the pathogenesis of microsatellite instability in Indian CRC. In the preliminary studies, we conducted a Nanostring Pan-Cancer pathway analysis of early-stage CRC (n = 10, MSS = 5, MSI = 5) and normal tissues (n=7). We identified the differentially expressed genes associated with the tumor and correlated them against microsatellite instability status. Among them, _AXIN2_, _ETV4_, and _RNF43_ were tumor cell-specific signals that had a differential expression between MSI and MSS groups. When overlapped with the TCGA immune cell infiltration data, TIMER, these genes segregated to the tumor cells. Moreover, they were less associated with other significant genes in protein-protein interaction analysis by STRING. The expression of these genes was further validated in another set of early-stage microsatellite instable CRC (n = 15) by qPCR. The expression fold-changes of these signals suggest distinct subsets in the MSI subgroup of CRC in the Indian population.