基底膜相关基因对肾细胞癌预后及临床的意义  

Prognostic model of renal cell carcinoma based on basement membrane-associated genes and its clinical significance

作　　者：陶华平 张烨 刘修恒[1] Tao Huaping;Zhang Ye;Liu Xiuheng(Department of Urology,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]武汉大学人民医院泌尿外科,武汉430060

出　　处：《国际泌尿系统杂志》2024年第6期1074-1079,共6页International Journal of Urology and Nephrology

基　　金：国家自然科学基金项目(81972408)。

摘　　要：目的探讨基底膜(BM)相关基因对肾细胞癌(RCC)预后及临床的意义。方法从TCGA和ICGC数据库中下载mRNA和临床信息,进行单因素和多因素Cox回归分析和LASSO回归分析以确定RCC患者的预后基因,随后构建预测RCC预后的风险模型。根据风险评分的中位数,将RCC患者分为高风险组和低风险组,采用Kaplan-Meier分析其预后情况,并在GDSC数据库中探讨两组之间药物敏感性的差异以及临床意义。结果TCGA数据库分析确定了109个BM相关基因在RCC中存在表达差异,选择差异最显著的50个基因进行可视化处理。单因素Cox回归分析结果显示,有18个BM相关基因对RCC患者具有预后价值。进一步使用LASSO Cox回归分析构建预测RCC患者预后的特征,最终确定了15个基因,并成功构建了风险模型。高风险组的死亡人数高于低风险组(P<0.001),时间依赖的受试者工作特征曲线(ROC)分析结果显示,基于BM相关基因模型预测1、3和5年生存率的曲线下面积(AUC)分别为0.722、0.696和0.700。随着肿瘤分级、T期、N期和病理分期的增加,风险评分显著提高(均P<0.001)。通过STRING数据库的PPI网络确定了10个枢纽基因。通过分析GDSC数据库中的数据,发现高风险组患者对舒尼替尼、博舒替尼、顺铂、吉西他滨等药物的IC50值低于低风险组。高风险组患者对AKT抑制剂的IC50值高于低风险组。结论本研究在RCC患者中确定了BM相关基因的差异表达,构建了基于BM相关基因的模型并在RCC患者中验证了预后预测特征。此外,RCC患者的BM相关基因风险评分与常见药物敏感性具有相关性,具有重要的临床参考价值。ObjectiveTo investigate the prognostic as well as clinical significance of basement membrane(BM)associated genes for renal cell carcinoma(RCC).MethodsUnivariate and multivariate Cox regression analysis and LASSO regression analysis were performed by downloading mRNA and clinical information from TCGA and ICGC databases to identify prognostic genes and then construct a risk model to predict RCC prognosis.The RCC patients were stratified into high-risk and low-risk groups according to the median risk score.Kaplan-Meier analysis was used to assess the prognosis between the high-risk and low-risk groups and to explore the differences in drug sensitivity between the two groups and the clinical significance in the GDSC database.ResultsTCGA database analysis identified 109 basement membrane-associated genes with differential expression in RCC,and the 50 genes with the most significant differences were selected for visualization.One-way Cox regression analysis showed that 18 basement membrane-related genes had prognostic value for RCC patients.LASSO Cox regression analysis was further used to construct features predicting the prognosis of RCC patients,and 15 genes were finally identified and successfully constructed a risk model.The number of deaths in the high-risk group was significantly higher than that in the low-risk group(P<0.001),and the results of time-dependent subject operating characteristic curves(ROC)showed that the areas under the curve(AUC)based on the BM-associated gene models predicting 1-year,3-year,and 5-year survival were 0.722,0.696,and 0.700,respectively.with the increase of tumor grading,T-stage,N-stage,and pathologic stage,the risk score significantly increased(all P<0.001).Ten pivotal genes were identified through the PPI network of the STRING database.By analyzing the data in the GDSC database,it was found that the IC50 values of patients in the high-risk group were lower than those in the low-risk group for sunitinib,bosutinib,cisplatin,and gemcitabine.On the contrary,patients in the high-risk

关 键 词：癌 肾细胞 基底膜相关基因 预后 

分 类 号：R737.11[医药卫生—肿瘤]