%0 Journal Article
%T Molecular pathogenesis of microsatellite instability-high early-stage colorectal adenocarcinoma in India.
%A Ariyannur P
%A Menon VP
%A Pavithran K
%A Paulose RR
%A Joy RA
%A Vasudevan DM
%J Drug Metab Pers Ther
%V 0
%N 0
%D 2024 Jul 24
%M 39042905
暂无%R 10.1515/dmpt-2024-0033
%X <B>OBJECTIVE: </B>The prevalence of microsatellite instability (MSI) subtype among all colon cancers in India is about 30 %, approximately two times more than that of western population suggesting different molecular pathogeneses.<BR><B>METHODS: </B>A NanoString analysis-based Pan cancer differential expression (DE) profile was determined in a primary cohort of early-stage CRC (tumor=10, normal=7), and correlated against MSI status. Using RT-PCR, tumor-specific DE genes were validated in another cohort of MSI-high CRC (n=15).<BR><B>RESULTS: </B>Among the most differentially expressed genes, AXIN2, ETV4, and RNF43 were tumor cell-specific signals, while a set of genes including COL11A1, COMP, INHBA, SPP1, MMP3, TLR2, and others were immune cell-specific signals, that had a differential expression between MSI and MSS groups. When overlapped with The Cancer Genome Atlas (TCGA) studies using the Tumor immune estimation resource tool (TIMER), and protein-protein interaction analysis by STRING.db, these genes were segregated to representative tumor cells and immune cells. On validation, the tumor-specific gene signals were inversely associated with TLR4 expression.<BR><B>CONCLUSIONS: </B>The differential expression distribution of AXIN2, ETV4, and RNF43 among tumor and immune cells, suggests more than one pathological subset in the MSI-H subgroup of early-stage CRC in the Indian population.