m6A RNA Methylation Regulators de fine tumor microenvironment and predict prognosis  in hepatocellular carcinoma

Abstract N6-methyladenosine (m6A) modification is considered to be the most significant and abundant mRNA modification and constitutes a critical mechanism of epigenetic regulation in various tumors. However, the potential influences of these m6A regulators on the tumor immune microenvironment (TIME) and immunotherapy in hepatocellular carcinoma (HCC) remain unknown. The present research aims to explore the roles of 38 m6A regulators in HCC. We investigated the different expression patterns of the m6A regulators between normal and HCC samples. Through consensus clustering of m6A regulators, three subgroups associated with patient survival and the infiltration of immune cells were recognized. Additionally, we constructed an m6A score model based on the m6A phenotype-related differentially expressed genes (DEGs) to quantify the m6A-related subtypes of individual tumors. Patients with a low m6Ascore had a better survival rate than those with a high m6Ascore, and patients with a high TMB and high m6Ascore had a worse survival rate. Moreover, patients in the high m6Ascore group had higher PD-L1 expression than the low m6Ascore group. The low m6Ascore group showed higher immune checkpoint inhibitor responses, including anti-CTLA-4 therapy, anti-PD-1, or a combination of both, than the high m6Ascore group. In conclusion, our study revealed the potential function of these mRNA modifications in TIME and identified their immunotherapeutic value.