Comprehensive analysis of mA regulator-based methylation modification patterns characterized by distinct immune profiles in colon adenocarcinomas.

Mounting evidences have indicated that RNA N-methyladenosine (mA) modification played important roles in tumor formation and growth. However, it is rarely reported that mA modifications are involved in the immune regulation and tumor microenvironment (TME) formation. In this study, we aimed to investigate the correlation between mA modifications and TME regulation of colon adenocarcinoma (COAD) by bioinformatic analysis. NMF algorithm was applied to carry out consensus molecular subtype analysis on 36 selected mA regulators regarding methylation modification, to identify mA modification patterns and characteristics of mA related genes in colon adenocarcinoma (COAD). Further, the relative infiltration levels of different immune cell subsets were quantified by ssGSEA and CIBERSORT algorithms, and a mSig scoring scheme was constructed to predict the prognosis and evaluate the response to immunotherapy in the patients with COAD. Among 579 COAD samples, we identified three different mA modification patterns which were related to different biological pathways and clinical outcomes. Then, a scoring scheme termed "mSig score" was developed based on mA-related characteristic genes, and was utilized to score patients with COAD into groups. We found that COAD patients with lower mSig scores exhibited prolonged survival and potentiated immune infiltration, which were associated with higher tumor mutation load, lower PD-L1 expression, and higher mutation rates of SMG (such as TTN and KRAS). Moreover, analysis regarding evaluation of immune response revealed that the patients with lower mSig scores had higher Immunophenoscore. Collectively, our study provided in depth insight into the interactions between mA modification and regulation of TME. In addition, the quantitative evaluation of mA modification patterns in our results may have implications in further immunotherapy for individual COAD patients.