m6A modification patterns and tumor immune landscape in clear cell renal carcinoma.

BACKGROUND: Recent studies have focused on the correlation between N6-methyladenosine (m6A) modification and specific tumor-infiltrating immune cells. However, the potential roles of m6A modification in the tumor immune landscape remain elusive. METHODS: We comprehensively evaluated the m6A modification patterns and tumor immune landscape of 513 clear cell renal cell carcinoma (ccRCC) patients, and correlated the m6A modification patterns with the immune landscape. The m6Ascore was established using principal component analysis. Multivariate Cox regression analysis was performed to evaluate the prognostic value of the m6Ascore. RESULTS: We identified three m6Aclusters-characterized by differences in Th17 signature, extent of intratumor heterogeneity, overall cell proliferation, aneuploidy, expression of immunomodulatory genes, overall somatic copy number alterations, and prognosis. The m6Ascore was established to quantify the m6A modification pattern of individual ccRCC patients. Further analyses revealed that the m6Ascore was an independent prognostic factor of ccRCC. Finally, we verified the prognostic value of the m6Ascore in the programmed cell death protein 1 (PD-1) blockade therapy of patients with advanced ccRCC. CONCLUSIONS: This study demonstrated the correlation between m6A modification and the tumor immune landscape in ccRCC. The comprehensive evaluation of m6A modification patterns in individual ccRCC patients enhances our understanding of the tumor immune landscape and provides a new approach toward new and improved immunotherapeutic strategies for ccRCC patients.