Molecular Characterization of m6A Modifications in Non-Clear Cell Renal Cell Carcinoma and Potential Relationship with Pathological Types

BACKGROUND: N6-Methyladenosine (m6A) modification is a eukaryotic mRNA modification that modulates the fate of modified RNA and, therefore, the expression of proteins. m6A modifications are associated with important roles in several cancers. Most studies related to m6A modification are based on clear cell renal cell carcinoma (ccRCC) and little is known about its role in non-ccRCC. METHODS: We summarized the molecular features of different m6A modification patterns in non-ccRCC based on The Cancer Genome Atlas database and correlated them with phenotypes such as immune patterns and prognosis. We also computed the m6Ascore and assessed its prognostic value using multivariate Cox regression analysis. RESULTS: We found the immune-excluded phenotype to be predominant in non-ccRCC patients. We also found that in non-clear cell carcinoma, different m6A modification profiles determine different immune patterns and are associated with different prognosis. m6AgeneCluser typing strongly associated with pathological status. Based on our findings, we suggest that the m6Ascore can be used as an independent prognostic value for prognostic assessment in non-ccRCC. CONCLUSION: This study confirms the important role of m6A modifications in non-ccRCC, reveals the heterogeneity of tumor immunity, and highlights the promise of non-ccRCC therapy.