TMB在肾透明细胞癌中的临床意义

Clinical significance of tumor mutation burden in renal clear cell carcinoma

目的研究肿瘤突变负荷(TMB)在肾透明细胞癌患者中的临床意义。方法通过癌症基因组图谱获取肾透明细胞癌的体细胞突变数据、基因表达数据甲基化数据和相关临床数据以及临床蛋白质组肿瘤分析协作组数据库中肾透明细胞癌的蛋白组数据,计算肾透明细胞癌患者的TMB值并分析TMB与总生存率的关系及其与临床预后的关系。TMB值按降序排列,以中位数将所有肿瘤样本分为高TMB组(171例)和低TMB组(166例),对两组的基因表达数据进行基因富集分析,对肾透明细胞癌突变率最高的前10位基因进行多组学分析。结果高TMB组患者的总生存率低于低TMB组(P=0.035);肿瘤级别越高的ccRCC患者的TMB值越高,差异有统计学意义(P=0.036)。突变率最高的前10位基因中,突变数据和预后相关的只有BAP1和HMCN1;SETD2、HMCN1、MTOR、PBRM1、MUC16的基因表达与ccRCC患者的临床预后相关;BAP1、DNAH9、HMCN1、KDM5C、MTOR的甲基化水平与ccRCC患者的临床预后相关。结论高TMB的肾透明细胞癌患者预后较差,不同肿瘤分级患者的TMB值不同,其突变率最高的前10位基因在突变水平、转录组水平以及甲基化水平与肾透明细胞癌患者预后相关。

Objective To study the clinical significance of tumor mutation burden(TMB)in patients with renal clear cell carcinoma.Methods The somatic mutation data,gene expression data,methylation data and related clinical data of renal clear cell carcinoma were obtained through the Cancer Genome Atlas,as well as the proteome data of renal clear cell carcinoma in Clinical Proteomic Tumor Analysis Consortium.The TMB value of patients with renal clear cell carcinoma was calculated,and the relationship between TMB and overall survival rate and clinical prognosis was analyzed.All tumor samples were divided into high TMB group(171 cases)and low TMB group(166 cases)in descending order,and the gene expression data of the two groups were analyzed by gene enrichment analysis,and the top 10 genes with the highest mutation rate of renal clear cell carcinoma were analyzed by multiomics.Results The overall survival rate of patients in the high TMB group was lower than that in the low TMB group(P=0.035),and the TMB values of different tumor grades were different(P=0.036).Among the top 10 genes with the highest mutation rate,only BAP1 and HMCN1 were associated with the prognosis.The expression of 5 genes:SETD2,HMCN1,MTOR,PBRM1 and MUC16 were correlated with the clinical prognosis of ccRCC patients.The methylation levels of five genes,BAP1,DNAH9,HMCN1,KDM5C and MTOR were correlated with the clinical prognosis of ccRCC patients.Conclusions The prognosis of renal clear cell carcinoma patients with high TMB is poor.The TMB value of tumor grade is different.The mutation level,transcriptome level and methylation level of the top 10 genes with the highest mutation rate are related to the prognosis of renal clear cell carcinoma patients.