Application of m6A and TME in Predicting the Prognosis and Treatment of Clear Cell Renal Cell Carcinoma

Abstract

Background. Previous studies have shown that RNA N6-methyladenosine (m6A) plays an important role in the construction of the tumor microenvironment (TME). However, how m6A plays a role in the TME of clear cell renal cell carcinoma remains unclear. Methods. Based on 23 m6A modulators, we applied consensus cluster analysis to explore the different m6A modification profiles of ccRCC. The CIBERSORT method was employed to reveal the correlation between TME immune cell infiltration and different m6A modification patterns. A m6A score was constructed using a principal component analysis algorithm to assess and quantify the m6A modification patterns of individual tumors. Results. Three distinct m6A 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 m6A scores were high, TME was characterized by immune cell infiltration and patient survival was higher ( p < 0.05 ). When m6A scores were low, TME was characterized by immunosuppression and patient survival was lower ( p < 0.05 ). The immunotherapy cohort confirmed that patients with higher m6A scores had significant therapeutic advantages and clinical benefits. Conclusions. The m6A modification plays an important role in the formation of TME. The m6A scoring system allows the identification of m6A modification patterns in individual tumors, discriminates the immune infiltrative features of TME, and provides more effective prognostic indicators and treatment strategies for immunotherapy.

TNBC Molecular Subtypes and Risk Signatures Based on Copper Metabolism: Prognostic and Immunological Importance

“…CRG cluster A, from a lack of an immune cell presence, had more of an immune-desert phenotype and was characterized as higher abundance of myeloid cells like monocytes, M0 macrophage cells, and M2 macrophage cells. CRG cluster B, however, was more in line with an immunoin ammatory phenotype because of the large degree of immune cell in ltration in the TME [21]. This was consistent with our nding that the cluster A group patients had worse prognoses compared with cluster B.…”