基于TCGA数据库分析肝细胞肝癌组织中HMMR表达与患者临床特征及预后的相关性  

The correlation between the expression of HMMR and clinical characteristics and prognosis of hepatocellular carcinoma based on TCGA database

作　　者：王敏 陈泽峰 韩志伟 邬国斌[1] 陈闯[1] 黄山[1] 赵荫农[1] WANG Min;CHEN Zefeng;HAN Zhiwei;WU Guobin;CHEN Chuang;HUANG Shan;ZHAO Yinnong(Guangxi Medical University Affiliated Tumor Hospital,Guangxi Nanning 530021,China)

机构地区：[1]广西医科大学附属肿瘤医院,广西南宁530021

出　　处：《现代肿瘤医学》2021年第7期1173-1178,共6页Journal of Modern Oncology

基　　金：中央引导地方科技发展专项(编号:桂科ZY1949017);广西高校中青年教师基础能力提升项目(编号:2018KY0126)。

摘　　要：目的:研究透明质酸介导的运动受体(hyaluronan-mediated motility receptor,HMMR)的表达与肝细胞肝癌(hepatocellular carcinoma,HCC)的发生发展以及预后的关系。方法:在本研究中,我们通过从癌症基因组图谱(the cancer genome atlas,TCGA)数据库中下载HCC有关的数据进行生物信息学分析,探讨HMMR表达在HCC发生、发展和预后中的价值。根据HMMR mRNA表达的中位值将患者分为两组(HMMR高表达组和HMMR低表达组),应用Kruskal-Wallis检验和Logistic回归分析HMMR表达与患者临床特征之间的关系,利用Kaplan-Meier和Cox分析观察HMMR表达对HCC患者生存的影响,并进行PPI蛋白互作网络、GO富集和KEGG通路分析。最后通过实时荧光定量PCR(quantitative real-time PCR,qRT-PCR)验证HMMR mRNA在HCC组织样本中的表达。结果:HCC组织中HMMR的高表达与组织学分级(G_(3) vs G_(1),OR=2.675)、癌组织阶段(ⅢvsⅠ,OR=2.509)、T分期(T_(4) vs T_(1),OR=3.568)相关(P均<0.05)。Kaplan-Meier生存分析显示,HMMR高表达的HCC预后比HMMR低表达的患者差(P=6.858E-05)。Cox分析显示HMMR高表达是总体生存(overall survival,OS)的危险因素(HR:1.166,95%CI:1.027~1.324,P=0.018)。PPI蛋白互作、GO富集和KEGG通路分析鉴定了与HMMR存在相互作用的10个基因,分别为:FAM83D、CD44、TPX2、PLK4、AURKA、PLK1、NEK2、CDK1、BUB1及DLGAP5,它们主要富集在有丝分裂细胞周期相变的调控、细胞周期过程、ECM-受体相互作用、FoxO信号通路、EB病毒感染等。qRT-PCR结果显示,HMMR mRNA在HCC癌组织中高表达(P<0.05)。结论:HMMR mRNA的高表达与HCC的发生发展密切相关,是HCC预后不良的独立危险因素。Objective:To investigate the relationship between the expression of hyaluronan mediated motility receptor(HMMR)and the occurrence,development and prognosis of hepatocellular carcinoma(HCC).Methods:In this study,we performed bioinformatics analysis by downloading hepatocellular carcinoma-related data from the cancer genome atlas(TCGA)database,and explored the value of HMMR expression in the occurrence,development and prognosis of hepatocellular carcinoma.According to the median value of HMMR mRNA expression,the patients were divided into two groups(HMMR group with high expression and HMMR group with low expression).The relationship between HMMR expression and clinical characteristics was analyzed by Kruskal-Wallis test and Logistic regression,and the influence of HMMR expression on the survival of patients with hepatocellular carcinoma was observed by Kaplan-Meier and Cox analysis.Moreover,PPI protein interaction network,GO enrichment and KEGG pathway analysis were performed.Finally,quantitative real-time PCR(qRT-PCR)was used to verify the expression ofHMMR mRNA in HCC tissue samples.Results:The high expression of HMMR in hepatocellular carcinoma was associated with histological grade(OR=2.675 for G_(3) vs G_(1)),clinical stage(OR=2.509 forⅢvsⅠ)and T stage(OR=3.568 for T_(4) vs T_(1))(all P<0.05).Kaplan-Meier survival analysis showed that HCC with HMMR high had a worse prognosis than that with HMMR-low(P=6.858E-05).Cox analysis showed that HMMR high expression was a risk factor for overall survival(OS)(HR:1.166,95%CI:1.027~1.324,P=0.018).PPI protein interactions,GO enrichment,KEGG pathway analysis,identify the interactions with HMMR 10 genes,respectively were:FAM83D,CD44,TPX2,PLK4,AURKA,PLK1,NEK2,CDK1,BUB1,DLGAP5,their main enrichment in regulation of mitotic cell cycle phase transition,cell cycle process,ECM-receptor interaction,FoxO signaling pathway and Epstein-Barr virus infection,etc.qRT-PCR results showed that HMMR mRNA was highly expressed in hepatocellular carcinoma(P<0.05).Conclusion:The high expressi

关 键 词：生物信息学 肝细胞肝癌 HMMR 预后 生物标志物 

分 类 号：R735.7[医药卫生—肿瘤]