Integrated Analyses of m⁶A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment...

The invasion of immune cells in the tumor microenvironment (TME) is closely related to cancer development. Studies have demonstrated that N6-methyladenosine (m⁶A) can affect the invasion of immune cells in TME as well as cancer development. We comprehensively analyzed the RNA-seq data of 16 different cancer types based on 20 m⁶A regulators and identified two distinct m⁶A modification patterns, which were closely associated with TME cell infiltration and overall patient survival. Then, we used principal component analysis (PCA) to construct m6Ascore based on the expression of m⁶A-related prognostic genes, which can successfully predict patient survival. The low-m6Ascore subtype is characterized by more immune cell infiltration, good prognosis and lower TNM stages, while the high-m6Ascore subtype is characterized by low immune infiltration, stromal activation, and poor prognosis. m6Ascore was also closely associated with immunotherapy response and was significantly higher in complete response/partial response (CR/PR) patients than in stable disease/progressive disease (SD/PD) patients in both immunotherapy cohorts. Therefore, our study indicates that m⁶A modification plays an important role in the prognosis of pan-cancer and the formation of complex TME in pan-cancer. Our research helps to improve the cognition of m⁶A modifications at pan-cancer levels and identify more effective strategies for immunotherapy.