Regulation of gene expression by DNA methylation with cytotoxic T lymphocytes evaluation in consensus molecular subtypes of colorectal cancer

Background: Low cytotoxic T lymphocyte (CTLs) infiltration in colorectal cancer (CRC) tumors is a challenge to treatment with immune checkpoint inhibitors. Consensus molecular subtypes (CMS) classify patients based on tumor attributes, and CMS1 patients include the majority of patients with high CTL infiltration and “inflamed” tumors. Epigenetic modification plays a critical role in gene expression and therapy resistance. Therefore, in this study we compared DNA methylation, gene expression, and CTL infiltration of CMS1 patients to other CMS groups to determine targets for improving immunotherapy in CRC. Furthermore, we used transcriptome of 91,103 unsorted scRNAseq to validate bulk RNA finding.

Results update: TBX21(T-bet) was the only gene highly correlated with CTL scores with differential gene expression and methylation in CMS2-4 when compared to CMS1. The patients with high TBX21 mRNA expression and low methylation has the best survival. The scRNAseq helped to confirm that T-bet may be a critical regulator of T cell responses in CRC.

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