Identification of cross-talk between m6A/m5C regulators and ferroptosis associated with immune infiltration and prognosis in pan-cancer
Abstract Although it has been recognized that m6A/5mC methylation and ferroptosis play critical roles in different types of cancers, little is known about the relationship between them. In addition, there is also a growing appreciation that m6A/5mC methylation and ferroptosis may affect immune cell infiltration and activation. This study aimed to reveal the extensive cross-talk between epigenetic modification and ferroptosis. A total of 31 cancer type-specific datasets in TCGA were individually collected by the publicly available web servers for multiple bioinformatic analyses of m6A/5mC regulators and ferroptosis-related genes. Intriguingly, m6A/5mC regulators and ferroptosis-related genes were identified to have considerable global coverage and prognostic significance across multiple cancer types. Moreover, m6A/5mC regulators showed interactive potential with ferroptosis-related genes, and genomic alteration of ferroptosis-related genes coupled with m6A/5mC regulators, at least in pancreatic cancer. Furthermore, m6A/5mC regulators and ferroptosis-related genes were found to be significantly associated with TILs. Finally, m6A/5mC regulators and ferroptosis-related genes exhibited functionally related to each other or co-regulated by TF or non-coding RNA. Together, m6A/5mC methylation and ferroptosis show a wide-ranging connection, and a combination strategy of epigenetic and ferroptosis therapies with ICP inhibitors may benefit more cancer patients in the future.