Pan-Cancer Analysis Links Altered RNA m7G Methyltransferase Expression to Oncogenic Pathways, Immune Cell Infiltrations and Overall Survival.

Abstract

N7-methylguanosine (m7G) modification is one of the most prevalent RNA modifications in humans. Dysregulated m7G modifications caused by aberrant expression of m7G writers contribute to cancer progression and result in worse patient survival in several human cancers. However, studies that systematically assess the frequency and clinical relevance of aberrant m7G writer expression in a pan-cancer cohort remain to be performed. This study aims to systematically investigate the molecular alteration and clinical relevance of m7G methyltransferase in human cancers. We analysed genome, transcriptome and clinical data from the Cancer Genome Atlas Research Network spanning 33 types of human cancers for aberrant changes in genes encoding m7G writers. We demonstrate that m7G writers are dysregulated in human cancers and are associated predominantly with poorer survival. By dividing patients into those with high and low m7G scores, we show that a lower m7G score is generally associated with immune infiltration and better response to immunotherapy. Our analyses indicate the genetic alterations, expression patterns and clinical relevance of m7G writers across various cancers. This study provides insights into the potential utility of m7G writer expression as a cancer biomarker and proposes the possibility of targeting m7G writers for cancer therapy.