Interplay of RNA m⁶A Modification-Related Geneset in Pan-Cancer

Background: N⁶-methyladenosine (m⁶A), is the most common modification found in mRNA and lncRNA in higher organisms and plays an important role in physiology and pathology. However, its role in pan-cancer has not been explored. Results: A total of 31 m⁶A modification regulators, including 12 writers, 2 erasers, and 17 readers are identified in the current study. The functional analysis of the regulators results in the enrichment of processes, primarily related to RNA modification and metabolism, and the PPI network reveals multiple interactions among the regulators. The mRNA expression analysis reveals a high expression for most of the regulators in pan-cancer. Most of the m⁶A regulators are found to be mutated across the cancers, with ZC3H13, VIRMA, and PRRC2A having a higher frequency rate. Significant correlations of the regulators with clinicopathological parameters, such as age, gender, tumor stage, and grade are identified in pan-cancer. The m⁶A regulators' expression is found to have significant positive correlations with the miRNAs in pan-cancer. The expression pattern of the m⁶A regulators is able to classify the tumors into different subclusters as well as into high- and low-risk groups. These tumor groups show differential patterns in terms of their immune cell infiltration, tumor stemness score, genomic heterogeneity score, expression of immune regulatory/checkpoint genes, and correlations between the regulators and the drugs. Conclusions: Our study provide a comprehensive overview of the functional roles, genetic and epigenetic alterations, and prognostic value of the RNA m⁶A regulators in pan-cancer.