The important role of N⁶-methyladenosine (m⁶A) RNA methylation regulator in carcinogenesis and progression of clear-cell renal cell carcinoma (ccRCC) is poorly understood by now. In this study, we performed comprehensive analyses of m⁶A RNA methylation regulators in 975 ccRCC samples and 332 adjacent normal tissues and identified ccRCC-related m⁶A regulators. Moreover, the m⁶A diagnostic score based on ccRCC-related m⁶A regulators could accurately distinguish ccRCC from normal tissue in the Meta-cohort, which was further validated in the independent GSE-cohort and The Cancer Genome Atlas-cohort, with an area under the curve of 0.924, 0.867, and 0.795, respectively. Effective survival prediction of ccRCC by m⁶A risk score was also identified in the Cancer Genome Atlas training cohort and verified in the testing cohort and the independent GSE22541 cohort, with hazard ratio values of 3.474, 1.679, and 2.101 in the survival prognosis, respectively. The m⁶A risk score was identified as a risk factor of overall survival in ccRCC patients by the univariate Cox regression analysis, which was further verified in both the training cohort and the independent validation cohort. The integrated nomogram combining m⁶A risk score and predictable clinicopathologic factors could accurately predict the survival status of the ccRCC patients, with an area under the curve values of 85.2, 82.4, and 78.3% for the overall survival prediction in 1-, 3- and 5-year, respectively. Weighted gene co-expression network analysis with functional enrichment analysis indicated that m⁶A RNA methylation might affect clinical prognosis through regulating immune functions in patients with ccRCC.

到目前为止，人们对N ^6-甲基腺苷（m ⁶ A）RNA甲基化调节剂在透明细胞肾细胞癌（ccRCC）的发生和发展中的重要作用还知之甚少。在这项研究中，我们对975 ccRCC样品和332个相邻正常组织中的m ⁶ A RNA甲基化调节剂进行了全面分析，并确定了与ccRCC相关的m ⁶ A调节剂。此外，基于ccRCC相关的m ⁶的m ⁶ A诊断得分监管机构可以准确区分ccRCC与Meta队列中的正常组织，这在独立的GSE队列和The Cancer Genome Atlas队列中得到了进一步验证，其曲线下面积分别为0.924、0.867和0.795。在癌症基因组图谱培训队列中还确定了通过m ⁶ A有效评估ccRCC的生存风险评分，并在测试队列和独立队列中进行了验证GSE22541生存率分别为3.474、1.679和2.101。通过单变量Cox回归分析，将m ⁶ A风险评分确定为ccRCC患者总体生存的危险因素，这在训练队列和独立验证队列中均得到了进一步验证。结合m ⁶ A风险评分和可预测的临床病理因素的综合列线图可以准确预测ccRCC患者的生存状况，其曲线下面积分别为1、3、3和83.2、82.4和78.3％和5年。加权基因共表达网络分析与功能富集分析表明，m ⁶RNA甲基化可能通过调节ccRCC患者的免疫功能来影响临床预后。