SLC22A8表达下调促进肾透明细胞癌代谢紊乱  

Downregulated expression of SLC22A8 promotes the metabolic disorders of clear cell renal cell carcinoma

作　　者：陈尚金 钟双泽 林汉胜 何京伟 CHEN Shangjin;ZHONG Shuangze;LIN Hansheng;HE Jingwei(The First Clinical College of Guangdong Medical University,Zhanjiang,Guangdong 524000,China;Department of UrologyⅡ,Yangjiang People's Hospital Affiliated to Guangdong Medical University,Yangjiang,Guangdong 529500,China)

机构地区：[1]广东医科大学第一临床医学院,广东湛江524000 [2]广东医科大学附属阳江人民医院泌尿外二科,广东阳江529500

出　　处：《安徽医药》2025年第1期74-78,I0003,I0004,I0005,共8页Anhui Medical and Pharmaceutical Journal

摘　　要：目的探索肾透明细胞癌(ccRCC)发生和进展的相关关键基因,研究其潜在的作用机制及预后价值。方法该研究于2022年11月始通过CEO2R在线分析工具对GEO数据库中的GSE6344和GSE53757进行差异表达基因(DEGs)的筛选并取交集得到共同差异表达基因,并在STRING数据库上构建蛋白质关系网络并应用Cytohubba插件取蛋白质作用关系程度TOP5的基因作为关键基因,之后通过生存分析得出与ccRCC预后相关的关键基因;应用cBioportal数据库进行基因改变分析得出显著突变的关键基因,DAVID数据库对显著突变关键基因进行功能富集与通路分析,UALCAN数据库和HPA数据库验证显著突变关键基因蛋白的差异表达,以上分析过程于2022年12月完成。结果GSE6344和GSE53757分别筛选出198个DEGs和183个DEGs并通过取交集获得63个共同差异表达基因(上调DEGs41个,下调DEGs22个);Cytohubba程序分析该63个基因的蛋白质关系网络得到五个关键基因:SMIM5、TMEM213、SLC12A3、SLC22A8、SLC13A3,均为下调基因;生存分析显示:SLC12A3、SLC22A8、SLC13A3、TMEM213与ccRCC预后相关;基因改变分析提示SLC22A8为显著突变的关键基因;富集分析主要与碳水化合物的代谢、线粒体功能以及过氧化物酶、氧化还原酶活性等多种调节过程相关。结论SLC22A8与肾透明细胞癌的预后密切相关,并通过代谢紊乱影响ccRCC的发生和进展,具有作为ccRCC治疗靶点的潜力。Objective To explore the key genes associated with the development and progression of clear cell renal cell carcinoma(ccRCC),and to study their potential effects and prognostic value.Methods From November 2022,the differentially expressed genes(DEGs)of GSE6344 and GSE53757 in the GEO database were screened by CEO2R online analysis tool to obtain common DEGs by intersection.Next,a protein interaction network were constructed by the STRING database and Cytohubba program was applied to select the genes with TOP5 protein interaction degree as key genes,following which these key genes were submitted to survival analysis to search which was associated with the prognosis of ccRCC.Subsequently,the cBioportal database was used for gene alteration analysis to derive significantly mutated key genes,DAVID database was used for functional enrichment and pathway analysis of key genes with significant mutations,and the differential expression of key gene proteins with significant mutations was confirmed in the UALCAN and HPA database.The above analysis process was completed on December 2022.Results There were 198 DEGs and 183 DEGs screened from GSE6344 and GSE53757,and 63 common DEGs(41 up-regulated genes and 22 down-regulated genes)were obtained by taking intersections.Furthermore,the protein relationship network of the 63 co-expressed DEGs was analyzed by applying Cytohubba program to obtain five key genes:SMIM5,TMEM213,SLC12A3,SLC22A8 and SLC13A3,all of which were down-regulated genes.Survival analysis revealed that SLC12A3,SLC22A8,SLC13A3 and TMEM213 were associated with ccRCC prognosis.The gene alteration analysis suggested that SLC22A8 was the key gene for prominent mutation and its enrichment analysis was mainly related to various regulated processes such as carbohydrate metabolism,mitochondrial function and peroxidase and oxidoreductase activities.Conclusion SLC22A8 is closely associated with the prognosis of ccRCC and affects its occurrence and development via metabolic disorders,having the potential as the therapeutic

关 键 词：肾肿瘤 差异基因表达 基因改变 关键基因 代谢紊乱 HPA数据库 

分 类 号：R737.11[医药卫生—肿瘤]