摘要
目的 探讨代谢相关基因在肾透明细胞癌(kidney renal clear cell carcinoma,KIRC)中的表达及与患者预后的关系,寻找潜在干预靶点。方法 利用生物信息学方法挖掘癌症基因图谱(Cancer Genome Atlas Program,TCGA)数据库中KIRC转录组数据,寻找在癌组织中异常表达的代谢相关基因(metabolism-related genes,MRGs),通过LASSO和Cox回归筛选与患者总生存期密切相关的代谢基因,进一步Cox回归构建患者预后风险评分模型并评价其预测能力。采用实时荧光定量PCR验证预后相关MRGs在人肾透明细胞癌A498细胞及肾小管上皮细胞HK-2的表达特征。结果 在KIRC与癌旁组织中差异表达的代谢相关基因共875个。单因素Cox回归分析显示38个MRGs显著影响患者预后,LASSO及多因素Cox回归分析进一步筛选出7个基因(CNGB1、CACNA1I、KCNT1、KCNH1、PLA2G4D、CHST6、ATP2A1)作为预后危险因素用于风险评分模型构建。患者风险评分可作为独立危险因子预测KIRC患者预后(风险比为4.671,P<0.001),而患者年龄、性别、肿瘤分级则与患者预后无相关性(P>0.05)。结论 KIRC中多个MRGs存在异常表达,从中筛选到7个基因并构建的代谢相关预后风险模型,可以有效预测KIRC患者预后,为KIRC临床诊疗提供新依据。
Objective To investigated the expression of metabolism-related genes(MRGs) in kidney renal clear cell carcinoma(KIRC) and its correlation with prognosis of patients so as to search for potential intervention targets.Methods Bioinformatics were used to mine KIRC transcriptome data in the Cancer Genome Atlas Program(TCGA) database,and the MRGs abnormally expressed were obtained,among which the ones closely associated with overall survival of KIRC patients were screened by LASSO and Cox regression.Furthermore,Cox regression analysis was adopted to construct a risk-score model to predict the prognosis of KIRC patients,and its predictive ability was evaluated.Finally,the expression characteristics of prognostic related MRGs were verified using RT-qPCR in KIRC cell line A498 and renal tubular epithelial cell line HK-2,respectively.Results A total of 875 differentially expressed MRGs were found between KIRC and adjacent tissues.Univariate Cox regression analysis showed that 38 MRGs significantly affected the prognosis of patients,and 7 of them(CNGB1,CACNA1I,KCNT1,KCNH1,PLA2G4D,CHST6,and ATP2A1) were further selected as prognostic risk factors by LASSO and multivariate Cox regression.Subsequently,a risk-score model was constructed based on the above 7 factors.The score obtained from the model could be used as an independent risk factor to predict the prognosis of KIRC patients(risk ratio:4.671,P0.05).Conclusion There are several MRGs with abnormal expression in KIRC,and the prognostic risk model based on 7 genes screened from the MRGs can effectively predict the prognosis of KIRC patients,providing a new basis for future diagnosis and treatment of KIRC.
作者
李德峰
毛杨
王文静
李园园
LI Defeng;MAO Yang;WANG Wenjing;LI Yuanyuan(Clinical Medical Research Center,Second Affiliated Hospital,Army Medical University(Third Military Medical University),Chongqing,400037,China)
出处
《陆军军医大学学报》
CAS
CSCD
北大核心
2023年第2期165-172,共8页
Journal of Army Medical University
基金
国家自然科学基金面上项目(31872634)。
关键词
肾透明细胞癌
代谢相关基因
预后模型
kidney renal clear cell carcinoma
metabolism-related genes
prognostic model
