摘要
目的探讨自噬相关基因RGS19在人类肝癌中的表达及其与临床病理特征和预后的关系。方法通过人类自噬数据库(HADb)、癌症基因组图谱(TCGA)、Oncomine等数据库分析自噬相关基因在肝癌组织和癌旁正常组织中表达水平的差异,最终筛选出RGS19作为靶基因。采用Wilcoxon秩和检验分析RGS19表达与肝癌临床病理特征的关系,生存分析采用Kaplan-Meier法,预后的单因素分析采用Log-rank检验,多因素分析采用Cox比例风险回归模型。通过STRING在线数据库构建RGS19蛋白相互作用网络,GSEA预测RGS19富集的生物学通路。结果对TCGA数据进行生物信息学分析显示,RGS19在肝癌组织中高表达(P<0.001),并在Oncomine数据库中得到验证。根据RGS19表达水平的中位值(3.41),将患者分为高表达和低表达两组,不同临床病理参数的RGS19表达水平进行比较,结果显示RGS19高表达与患者的年龄、肿瘤分级、临床分期和浸润深度有关(P<0.05)。RGS19高表达组的中位生存期(OS)为3.80年,明显短于低表达组的6.94年(P<0.05);Cox多因素回归分析显示,RGS19表达水平和临床分期是影响肝癌预后的独立因素(P<0.05)。蛋白相互作用网络预测了可能与RGS19相互作用的蛋白;GSEA分析表明RGS19主要富集在血管内皮生长因子(VEGF)信号通路、T细胞受体(TCR)信号通路、B细胞受体(BCR)信号通路、NOD样受体信号通路、丝裂原蛋白活化激酶(MAPK)信号通路和WNT信号通路中。结论RGS19是肝癌潜在的诊断和预后分子标志物,有望成为肝癌新的治疗靶点。
Objective To explore the expression of autophagy-related gene RGS19,as well as its clinical and prognosis value in human hepatocellular carcinoma(HCC).Methods The difference of expression level of autophagy-related genes in HCC tumor samples and adjacent normal samples were analyzed through Human Autophagy Database(HADb),The Cancer Genome Atlas(TCGA)and Oncomine databases,finally we screened out RGS19 as the target gene.The relationship between the expression of RGS19 and the clinicopatholical features of HCC was analyzed by Wilcoxon test.The Kaplan-Meier method and Log-rank test were conduceted for univariate analysis,and the Cox proportional hazard regression model was conducted for multivariate analysis.The RGS19 protein interaction network was constructed by STRING,and the biological pathway of RGS19 involved was predicted by GSEA.Results Bioinformatic analysis for TCGA datasets showed that RGS19 was highly expressed in HCC(P<0.001)and it was validated in Oncomine database.Patients were divided into high-expression and low-expression group according to the median value(3.41)of RGS19 expression level.Correlation analysis and Logistic regression showed that the high expression of RGS19 was significantly correlated with age,tumor grade,clinical stage and depth of invasion(P<0.05).The median overall survival of patients with RGS19 high-expression was 3.80 years,which was lower than 6.94 years of patients with low-expression(P<0.05).Cox regression analysis suggested that the expression level of RGS19 and clinical stage can be used as independent risk factors for the prognosis of HCC(P<0.05).Protein interaction network showed proteins that may interact with RGS19.GSEA predicted that the high expression of RGS19 was concentrated in VEGF signaling pathway,TCR signaling pathway,BCR signaling pathway,NOD-like receptor signaling pathway,MAPK signaling pathway and WNT signaling pathway.Conclusion RGS19 may be a potential diagnostic and prognostic biomarker for HCC,which could serve as a new therapeutic target for HCC pat
作者
庞晶晶
杨春秀
潘贺
肖书渊
PANG Jingjing;YANG Chunxiu;PAN He;XIAO Shuyuan(Department of Pathology,Zhongnan Hospital of Wuhan University,Wuhan 430000,China)
出处
《临床肿瘤学杂志》
CAS
2021年第9期808-815,共8页
Chinese Clinical Oncology
基金
武汉大学中南医院重点研发培育项目(znpy2019092)。
关键词
肝细胞癌
基因表达
预后
RGS19
Hepatocellular carcinoma
Gene expression
Prognosis
RGS19
