肾透明细胞癌中预后相关RNA编辑位点的筛选

Screening of prognosis-related RNA editing sites in clear cell renal cell carcinoma

目的探讨肾透明细胞癌(ccRCC)中与患者生存预后相关的RNA编辑位点。方法下载癌症基因组图谱(TCGA)中RNA编辑位点的表达数据,使用最小绝对收缩和选择算子(LASSO)及Cox回归筛选出与ccRCC预后密切关联的RNA编辑位点。根据多因素Cox结果计算患者的风险评分后构建预后模型和列线图,进一步采用接受者操作特征(ROC)曲线评估预后模型和列线图的准确性,并进行相关的功能学分析。结果共筛选出25个与ccRCC预后相关的RNA编辑位点。根据风险评分的中位值将患者分为高风险组(n=222)与低风险组(n=226)。Kaplan-Meier生存分析结果显示,高风险组患者的总生存时间与疾病无进展生存时间均低于低风险组(P<0.001)。预后模型和列线图预测患者1、3、5年生存的曲线下面积(AUC)值分别为0.801、0.824和0.806、0.858,0.833和0.821。风险分组之间具备不同的生物学功能及药物敏感性。结论通过公共数据库筛选出的25个RNA编辑位点有望会成为ccRCC患者新的预后标记物。

Objective To explore RNA editing sites associated with survival and prognosis in clear cell renal cell carcinoma(ccRCC).Methods After the expression data of RNA editing sites in the Cancer Genome Atlas(TCGA)were downloaded,the minimum absolute contraction,selection operator(LASSO)and Cox regression were used to identify RNA editing sites closely associated with ccRCC prognosis.A prognostic model and nomogram were constructed after the risk scores were calculated based on the multivariate Cox results.The accuracy of the prognostic model and nomogram was evaluated with the receiver operating characteristic(ROC)curve,and the relevant functional analysis was performed.Results A total of 25 RNA editing sites associated with ccRCC prognosis were screened.Patients were divided into the high-risk group(n=222)and low-risk group(n=226)based on the median risk score.Kaplan-Meier survival analysis showed that the overall survival(OS)and progression-free survival(PFS)were in shorter in the high-risk group than in the low-risk group(P<0.001).The area under the ROC curve(AUC)of 1-year,3-year and 5-year survival predicted by the prognosis model were 0.801,0.824 and 0.806,and those predicted by the nomogram were 0.858,0.833 and 0.821,respectively.There were differences in biological function and drug sensitivity between the two groups.Conclusion The 25 RNA editing sites are expected to become new prognostic markers and drug therapeutic targets for patients with ccRCC.