RNA Modification of N6-Methyladenosine Predicts Immune Phenotypes and Therapeutic Opportunities in Kidney Renal Clear Cell Carcinoma

RNA modification of N6-methyladenosine (m6A) plays critical roles in various biological processes, such as cancer development, inflammation, and the anticancer immune response. However, the role played by a comprehensive m6A modification pattern in regulating anticancer immunity in kidney renal clear cell carcinoma (KIRC) has not been fully elucidated. In this study, we identified two independent m6A modification patterns with distinct biological functions, immunological characteristics, and prognoses in KIRC. Next, we developed an m6A score algorithm to quantify an individual's m6A modification pattern, which was independently validated in external cohorts. The m6A cluster 1 and low m6A score groups were characterized by a hot tumor microenvironment with an increased infiltration level of cytotoxic immune cells, higher tumor mutation burden, higher immune checkpoint expression, and decreased stroma-associated signature enrichment. In general, the m6A cluster 1 and low m6A score groups reflected an inflammatory phenotype, which may be more sensitive to anticancer immunotherapy. The m6A cluster 2 and high m6A score groups indicated a non-inflammatory phenotype, which may not be sensitive to immunotherapy but rather to targeted therapy. In this study, we first identified m6A clusters and m6A scores to elucidate immune phenotypes and to predict the prognosis and immunotherapy response in KIRC, which can guide urologists for making more precise clinical decisions.