Tumor Microenvironment in Clear Cell Renal Cell Carcinoma: A Comprehensive Analysis.

BACKGROUND

M6A RNA methylation and the tumor microenvironment (TME) have been reported to play important roles in the progression and prognosis of clear cell renal cell carcinoma (ccRCC). However, whether m6A RNA methylation regulators affect the TME in ccRCC remains unknown. Thus, we aimed to evaluate comprehensively the effect of m6A RNA methylation regulators on the TME in ccRCC.

METHODS

Transcriptome data of ccRCC were obtained from TCGA database. Consensus clustering analysis was conducted based on the expression of m6A RNA methylation regulators. Survival differences were evaluated by Kaplan-Meier analysis between the clusters. The DESeq2 package was used to analyze the differentially expressed genes (DEGs) between the clusters. GO and KEGG pathway analyses were performed by the ClusterProfiler R package. The CIBERSORT algorithm was used to evaluate immune infiltration.

RESULTS

The expression of 15 m6A regulators significantly differed between ccRCC and normal kidney tissues. Based on the expression of these 15 m6A regulators, two clusters were identified by consensus clustering, in which cluster 1 had better overall survival (OS). Overall, 4,429 DEGs were identified between the two clusters and were enriched in immune-related biological processes. Cluster 1 had lower immune and ESTIMATE scores, higher expression of HLA and lower expression of immune checkpoint molecules. Moreover, immune infiltration and expressions of Th1/IFNγ gene signature were also significantly different between the two clusters.

CONCLUSION

Our study revealed m6A regulators were important participants in the development of ccRCC, with a close relationship with the TME.