基于生物信息学探讨GNB2L1基因在肝癌中的表达及其临床价值  

GNB2L1 gene expression and clinical value in hepatocellular carcinoma based on bioinformatics

作　　者：范玲燕 孙春丽 陈昱含 高国生 Fan Lingyan;Sun Chunli;Chen Yuhan;Gao Guosheng(Huamei Hospital,University of Chinese Academy of Sciences,Zhejiang Provincial Key Laboratory of Diagnosis,Treatment and Research of Digestive System Tumors,Ningbo 315010,China;Zhejiang University-University of Edinburgh Institute,Haining 314400,China;Atlanta Emory University,Atlanta 30322,USA)

机构地区：[1]中国科学院大学宁波华美医院浙江省消化系统肿瘤诊治及研究重点实验室,宁波315010 [2]浙江大学国际校区浙江大学爱丁堡大学联合学院,海宁314400 [3]美国亚特兰大埃默里大学,亚特兰大30322

出　　处：《中华肝脏病杂志》2022年第9期954-961,共8页Chinese Journal of Hepatology

基　　金：宁波市公益类科技计划项目(2019C50035);浙江省消化系统肿瘤诊治及研究重点实验室(2019E10020)。

摘　　要：目的基于生物信息学数据库分析G蛋白β2亚基类似物1(GNB2L1)基因在肝癌中的表达情况,评估其在肝癌发生、发展中的作用及其与生存率的关系。方法基于GEPIA、UALCAN和HPA数据库分析GNB2L1在肝癌中的表达水平以及其与生存率的关系;cBioPortal数据库分析GNB2L1基因的突变情况及其对生存率的影响;LinkedOmics数据库分析GNB2L1在肝癌中的相关基因,同时进行基因本体论(GO)功能注释、京都基因与基因组百科全书通路富集分析;STRING数据库构建GNB2L1蛋白相互作用网络;TIMER数据库分析GNB2L1基因表达与肝癌免疫浸润的关系。基于mRNA测序技术分析肝癌患者和健康对照血浆血小板中GNB2L1表达的差异。组间数据比较采用独立样本t检验。结果GNB2L1在肝癌组织中表达水平显著升高(P<0.05),其表达与体质量、肝癌分级和分期之间均存在显著相关性(P值均<0.05);GNB2L1低表达组的总体生存率更高(P<0.001)。GNB2L1及其相关基因可能与生物过程调节、代谢过程、蛋白结合、氧化磷酸化、JAK-STAT信号通路、Ras信号通路等相关。GNB2L1与核糖体蛋白S12、S11、L19等存在相互作用,参与了肝脏再生、内源性凋亡信号通路的正性调控等多个生物学过程。GNB2L1表达水平与肝癌中多种免疫细胞的浸润程度均有正相关(P值均<0.05),Cox回归分析结果显示GNB2L1是肝癌患者较低生存率的独立危险因素[风险比值比(95%可信区间)为1.456(1.034~2.051),P=0.031]。肝癌患者血小板中GNB2L1的表达水平显著高于健康对照组(10.40±1.36与9.58±0.51,t=2.194,P=0.037)。结论GNB2L1在肝癌中高表达且与生存率密切相关,GNB2L1可能是肝癌的潜在生物标志物。Objective To analyze guanine nucleotide-binding protein subunit beta-2-like 1(GNB2L1)expression based on bioinformatics,so as to evaluate its role and its relationship with survival rate during the occurrence and development of hepatocellular carcinoma.Methods GEPIA,UALCAN and HPA databases were used to analyze the expression level of GNB2L1 and its relationship with HCC survival rate.Mutations in the GNB2L1 gene and their impact on survival were analyzed using the cBioPortal database.LinkedOmics database was used to analyze GNB2L1-related genes in HCC.Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed simultaneously.STEING database was used to construct the GNB2L1 protein interaction network.TIMER database was used to analyze the relationship between GNB2L1 gene expression and immune infiltration in hepatocellular carcinoma.Differential expression of GNB2L1 in plasma platelets of HCC patients and healthy controls was analyzed using mRNA-based sequencing technology.Data between groups were compared using an independent-samples t-test.Results GNB2L1 expression level was significantly increased in HCC tissues(P<0.05),and its expression was significantly correlated with body weight,classification and stage(P<0.05).The overall survival rate was higher in GNB2L1 low expression group(P<0.001).GNB2L1 and its related genes were related to biological process regulation,metabolic process,protein binding,oxidative phosphorylation,JAK-STAT signaling pathway,Ras signaling pathway and so on.GNB2L1 had interaction with RPS12,RPS11 and RPL19,and participated in multiple biological processes such as liver regeneration and positive regulation of endogenous apoptotic signaling pathway.GNB2L1 expression was significantly positively correlated with the infiltration degree of various immune cells in HCC(P<0.05).Cox regression analysis showed that GNB2L1 was an independent risk factor for lower survival rate in patients with HCC[Hazard ratio(95%confidence interv

关 键 词：肝肿瘤 G蛋白β2亚基类似物1 生物信息学 数据库 

分 类 号：R735.7[医药卫生—肿瘤]