Comprehensive Analysis of M6A-Related lncRNAs, Immune Checkpoints and Immune Infiltrates in Clear Cell Renal Cell Carcinoma

Abstract Background Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer in the world and is strongly related to the tumor immune microenvironment (TIME), which is mediated by N6 Methyladenosine-related long noncoding RNAs (m6A-related lncRNAs). In order to explore the underlying effective treatment and prognostic biomarkers, the correlation of m6A-related lncRNA, TIME with survival deserves in-depth study. Methods All the data which include 53 tumor samples as well as 72 normal samples were obtained from The Cancer Genome Atlas (TCGA). Herein, we systematically explored the correlations of prominent m6A-related lncRNAs with 5 immune checkpoints (CTLA4, TIGIT, PDCD1, CD19 and LAG3) and immune infiltrates. Patients were divided into 2 clusters based on 30 prognostic m6A-related lncRNAs. Six m6A-related lncRNA-associated signatures were used to construct a risk model for ccRCC. Following that, we investigated the correlation between m6A-related lncRNA-associated signatures and immune cells, immune score, and immune checkpoints. Results The expressions of these 5 immune checkpoints (CTLA4, TIGIT, PDCD1, CD19 and LAG3) were positively correlated with the expressions of the 30 m6A-related lncRNAs. Compared to cluster 1, cluster 2 had a higher immunoscore, remarkable immune cell infiltration, upregulated checkpoints and poor prognosis. The hallmarks protein secret, androgen response, adipogenesis, bile acid metabolism, fatty acid metabolism and PPAR signaling pathway were remarkably enriched in the cluster 1. With high-risk scores, patients had higher immunoscore and higher expression of the 5 immune checkpoints. The amount of tumor-infiltrating immune cells was dynamically altered by copy-number changes in m6A-related lncRNA-associated signatures. Conclusions Our research revealed the crucial involvement of m6A-related lncRNAs in the TIME of ccRCC. The suggested m6A-related lncRNA-associated signatures might be important mediators of TIME in ccRCC, providing ideal therapeutic targets in immunotherapeutic effectiveness.