Application of mA and TME in Predicting the Prognosis and Treatment of Clear Cell Renal Cell Carcinoma.

Background: Previous studies have shown that RNA N6-methyladenosine (mA) plays an important role in the construction of the tumor microenvironment (TME). However, how mA plays a role in the TME of clear cell renal cell carcinoma remains unclear.

Methods: Based on 23 mA modulators, we applied consensus cluster analysis to explore the different mA modification profiles of ccRCC. The CIBERSORT method was employed to reveal the correlation between TME immune cell infiltration and different mA modification patterns. A mA score was constructed using a principal component analysis algorithm to assess and quantify the mA modification patterns of individual tumors.

Results: Three distinct mA modification patterns of ccRCC were identified. The characteristics of TME cell infiltration in these three patterns were consistent with immune rejection phenotype, immune inflammation phenotype, and immune desert phenotype. In particular, when mA scores were high, TME was characterized by immune cell infiltration and patient survival was higher ( < 0.05). When mA scores were low, TME was characterized by immunosuppression and patient survival was lower ( < 0.05). The immunotherapy cohort confirmed that patients with higher mA scores had significant therapeutic advantages and clinical benefits.

Conclusions: The mA modification plays an important role in the formation of TME. The mA scoring system allows the identification of mA modification patterns in individual tumors, discriminates the immune infiltrative features of TME, and provides more effective prognostic indicators and treatment strategies for immunotherapy.