透明细胞肾细胞癌预后标志物的生物信息学筛选和鉴定  

Screening and identification of prognostic markers for clear cell renal cell carcinoma with bioinformatics

作　　者：余祖虎 陆斌 高鸿 梁荣芳 刘京平 向五星 YU Zu-hu;LU Bin;GAO Hong;LIANG Rong-fang;LIU Jing-ping;XIANG Wu-xing(Department of Urology,University of Chinese Academy of Sciences-Shenzhen Hospital(Guangming),Shenzhen 518107,China)

机构地区：[1]中国科学院大学深圳医院(光明)泌尿外科,广东深圳518107

出　　处：《社区医学杂志》2022年第14期775-783,共9页Journal Of Community Medicine

基　　金：深圳市光明区卫生系统科研项目(2020R01034)

摘　　要：目的透明细胞肾细胞癌(ccRCC)是肾细胞癌的主要亚型,恶性程度高,预后差。应用生物信息学的方法,筛选并鉴定出ccRCC的预后标志物。方法利用基因表达数据库(GEO)中的3个基因数据集(GSE6344、GSE53757和GSE66270)筛选出ccRCC组织与相邻正常组织间的差异表达基因(DEGs),利用基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析对差异表达基因进行功能分析。用STRING数据库和Cytoscape软件构建差异表达基因蛋白之间相互作用网络并获取枢纽基因。利用UALCAN和GEPIA数据库对枢纽基因进一步筛选,获得与ccRCC预后相关的基因。利用GEPIA、UALCAN、CPTAC和HPA等数据库网站对候选基因进行mRNA和蛋白水平验证。结果经过筛选,共获得了163个在透明细胞肾癌组织和癌旁组织中表达量有明显差异的基因。通过进一步筛选及分析发现,与癌旁正常组织相比,ccRCC患者癌组织中果糖-1,6-二磷酸醛缩酶B(ALDOB)、溶质载体家族34成员A1(SLC34A1)、磷酸烯醇式丙酮酸羧激酶1(PCK1)和重组人脂肪酸结合蛋白1(FABP1)等基因的mRNA和蛋白表达量均显著下调。这些基因的低表达水平与ccRCC患者的总生存期和无病生存期不良有关。结论ALDOB、SLC34A1、PCK1和FABP1在ccRCC癌组织中表达下调,可能成为判断患者预后的标志物。Objective Clear cell renal cell carcinoma(ccRCC)is the main subtype of renal cell carcinoma with high malignancy and poor prognosis.In this study,we applied bioinformatics to screen and identify prognostic markers of ccRCC.Methods Three micro-array series(GSE6344,GSE53757,GSE66270)in gene expression omnibus database(GEO)database were used to screen differentially expressed genes(DEGs)between ccRCC tissues and adjacent normal tissues,gene ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis were performed to analyze the functions of differentially expressed genes.The protein-protein interaction network between differentially expressed genes was constructed with STRING database and Cytoscape software to obtain hub genes.The hub genes were further screened by UALCAN and GEPIA databases to obtain key genes related to the prognosis of ccRCC.The mRNA and protein levels of key genes were verified by databases such as GEPIA,UALCAN,CPTAC and HPA.Results After screening,a total of 163 genes which were differentially expressed in ccRCC tissues and adjacent normal tissues were obtained.Further screening and analysis indicated that the mRNA and protein expression levels of fructose-1,6-bisphosphate aldolase B(ALDOB),solute carrier family 34 member 1(SLC34A1),phosphoenolpyruvate carboxykinase 1(PCK1)and fatty acid-binding protein 1(FABP1)in cancer tissues of ccRCC patients were significantly down-regulated,compared with normal adjacent tissues.Low expressions of these genes were associated with poor overall survival and disease-free survival in ccRCC patients.Conclusion ALDOB,SLC34A1,PCK1 and FABP1 are significantly down-regulated in ccRCC tissues,they may be prognostic markers for ccRCC patients.

关 键 词：透明细胞肾细胞癌 生物信息学分析 果糖-1 6-二磷酸醛缩酶B 溶质载体家族34成员A1 磷酸烯醇式丙酮酸羧激酶1 重组人脂肪酸结合蛋白1 

分 类 号：R737.11[医药卫生—肿瘤] Q811.4[医药卫生—临床医学]