基于生物信息学分析γ-谷氨酰基环转移酶基因表达在胃癌中的意义  

Significance and mechanism of GGCT gene in gastric cancer based on bioinformatics

作　　者：余水红[1] 钱燕[1] 王晓梅[2] 龚莉 YU Shuihong;QIAN Yan;WANG Xiaomei;GONG Li(Research Center,Anqing Medical College,Anqing 246052,Anhui,P.R.China;School of Medicine,Shenzhen University,Shenzhen 518060,Guangdong,P.R.China;College of Life Sciences,Anqing Normal University,Anqing 246052,Anhui,P.R.China)

机构地区：[1]安庆医药高等专科学校科研中心,安徽安庆246052 [2]深圳大学医学院,广东深圳518061 [3]安庆师范大学生命科学学院,安徽安庆246502

出　　处：《滨州医学院学报》2021年第6期407-414,426,共9页Journal of Binzhou Medical University

基　　金：安徽省高等学校优秀人才项目(gxyq2021266);安徽省卫生健康委员会科技计划(AHWJ2021b117);安庆医药高等专科学校自然科学重点项目(ZR2019003)。

摘　　要：目的γ-谷氨酰基环转移酶(GGCT)是一种参与谷胱甘肽代谢的酶,异常表达的GGCT与多种肿瘤的发生发展紧密相关,但GGCT在胃癌中的潜在生物作用仍有待进一步挖掘。方法通过UALCAN和Oncomine数据库分析GGCT基因的转录水平,Kaplan-Meier plotter数据库分析GGCT基因表达与患者生存之间的关系、与不同临床病理特征胃癌患者预后的相关性,LinkedOmics数据库分析GGCT基因正负相关的网络基因,MetaScape数据库分析GGCT基因及网络基因功能注释及基因通路,最后结合TIMER数据库研究GGCT基因与免疫细胞浸润的相关性。结果胃癌组织中GGCT mRNA水平及DNA拷贝数高于相应的正常组织(P<0.05)。GGCT高表达组的总生存期、首次进展期及进展期明显长于低表达组(P<0.05)。高表达GGCT延长了单纯手术治疗患者、HER2阴性和HER2阳性患者、低分化以及II/III/IV期胃癌患者总生存期(P<0.05)。GGCT基因及相关网络基因参与了细胞周期、跨膜损伤运输、cGMP-PKG信号通路、肌肉收缩、Apelin信号通路和一氧化氮刺激鸟苷酸环化酶等过程。GGCT的表达与不同发育阶段的CD4^(+)T、CD8^(+)T细胞、巨噬细胞、中性粒细胞、树突状细胞浸润水平有一定的相关性。结论GGCT基因与胃癌患者的预后及免疫浸润有关,为进一步研究GGCT在胃癌中的作用奠定了基础。Objectiveγ-Glutamylcyclotransferase(GGCT)is an enzyme involved in glutathione metabolism.Abnormal GGCT expression is associated with carcinogenesis and development.The potential biological role of GGCT in gastric cancer(GC)remains to be determined.Methods This study assessed GGCT transcriptional levels using the Oncomine and UALCAN database.The correlation of GGCT expression with the survival and the clinicopathological characteristics of gastric cancer patients were analyzed via Kaplan-Meier plotter database.Positive and negative genes network with GGCT were identified using LinkedOmics.MetaScape was used to identify Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways.Finally,the correlation between the GGCT and tumor immunity was studied using TIMER.Results GGCT mRNA levels and DNA copy number were higher in gastric cancer tissues than those in normal tissues(P<0.05).Overall survival,first progression,and post progression in the high GGCT expression group were significantly longer than those in the low expression group(P<0.05).High GGCT expression had markedly improved overall survival in patients with surgery alone,HER2-negative and HER2-positive patients,poorly differentiated patients,and GC patients in stage II/III/IV(P<0.05).Functional network analysis revealed that GGCT and related network genes were involved in cell cycle,cGMP-PKG signaling pathway,muscle contraction,Apelin signaling pathway and translesion synthesis,etc.GGCT expression was closely associated with the immune-infiltrating levels,CD4^(+)T,CD8^(+)T,neutrophils,macrophages and dendritic cells.Conclusion These findings suggest that GGCT is correlated with prognosis and immune infiltrating in GC,laying a foundation for further study of the role of GGCT in GC.

关 键 词：胃癌 GGCT基因 数据库和价值 

分 类 号：R735.2[医药卫生—肿瘤]