N6-methyladenosine Methylation Related Immune Biomarkers Correlates With Clinicopathological Characteristics and Prognosis in Clear Cell Renal Cell Carcinoma

Abstract

\n Background: This study aimed to explore N6-methyladenosine (m6A) methylation-related immune biomarkers and their clinical value in clear cell renal cell carcinoma (ccRCC).Methods: The RNA-seq data and clinical phenotype of ccRCC were downloaded from TCGA database. Immune-related genes list was downloaded from InnateDB database. Correlation analysis, survival analysis, univariate and multivariate Cox regression analysis were used to investigate the prognostic independent m6A-related immune genes, followed by prognosis risk model establishment. Patients were divided into high/low risk groups, followed by survival analysis, clinical factors, immune checkpoint genes and gene set variation analysis in high-risk vs. low-risk group. Results: Five prognostic independent m6A-related immune genes (PKHD1, IGF2BP3, RORA, FRK and MZF1) were identified. Low expression of PKHD1, RORA and FRK were associated with poor survival, while high expression of IGF2BP3 and MZF1 were associated with poor survival for ccRCC patients. Their expression showed correlations with multiple m6A genes. The risk model could stratify ccRCC patients into high/low risk group, and patients with high-risk were associated with short survival time. High-risk group had an high proportion of patients in tumor stage Ⅲ-Ⅳ and patients with pathologic T3-T4 tumors, lymph node metastasis (N1) and distant metastasis (M1). Ten immune checkpoint genes were differentially expressed in high/low risk groups, such as PD1 and CTLA-4. The risk group could be an independent prognostic factor (HR=1.69, 95% CI 1.07-2.68, P=0.0246). Conclusion: In this study, we developed a five genes risk model, which had independent prognostic value and associated with tumor stage, pathologic T/N/M and immune checkpoint expression in ccRCC.