ESPL 1基因在肝细胞癌组织中的表达及其在预后评估中的作用

Expression of ESPL 1 gene in hepatocellular carcinoma tissue and its role in the prognosis assessment

目的探讨外纺锤体极样蛋白1(ESPL 1)基因在肝细胞癌(HCC)中的表达及其对临床预后的影响,初步分析ESPL 1变异情况及分子生物学功能。方法从TCGA数据库获得HCC患者ESPL 1表达数据和临床信息,比较癌、癌旁及正常组织中ESPL 1的表达情况。采用Cox回归分析影响HCC患者预后的危险因素,Kaplan-Meier法分析ESPL 1表达水平与HCC患者预后的关系。log rank检验ESPL 1高表达组和低表达组的生存差异。cBioportal在线软件分析ESPL 1突变情况,通过STRING数据库绘制ESPL 1蛋白互作网络,并据此进行GO|KEGG富集分析其分子生物学功能。结果肝癌组织中ESPL 1表达水平高于癌旁及正常组织,分别为0.894±0.643比0.337±0.340、1.908±1.079比0.912±0.770(P<0.05);乙型肝炎相关肝癌ESPL 1水平高于非乙型肝炎相关肝癌,为2.159±1.17比1.747±0.983(P<0.05)。ESPL 1表达水平与性别、年龄、BMI、原发肿瘤分期、AFP水平有关(P<0.05)。原发肿瘤分期、ESPL 1表达水平是HCC患者预后的独立危险因素,ESPL 1表达越高,预后越差(HR=1.72,95%CI:1.21~2.41,P<0.05)。ESPL 1在HCC患者中突变率为1%,突变者预后较差。富集结果显示ESPL 1主要参与细胞周期、有丝分裂、染色体分离等生物学功能。结论ESPL 1在HCC中表达上调,尤其在乙型肝炎相关肝癌中高表达具有特异性。HCC患者ESPL 1高表达及存在ESPL 1突变者预后较差。ESPL 1可作为HCC患者不良预后的潜在标志物。

Objective To investigate the expression of Extra spindle poles-like 1 protein(ESPL 1)gene in hepatocellular carcinoma(HCC)tissues and its influence on clinical prognosis of HCC,and preliminarily analyze the variation and molecular biological function of ESPL 1.Methods ESPL 1 expression data and clinical information of HCC patients were obtained from the TCGA database.The expression levels of ESPL 1 in cancer,paracancerous,and normal tissues were compared.The COX regression was used to investigate the risk factors of the prognosis in HCC patients,and the Kaplan-Meier method was used to investigate the relationship between the high and low ESPL 1 expression level and the prognosis of HCC patients.According to the median ESPL 1 expression level,the data were divided into high-expression group and low-expression group,and the log rank test was used to analyze the survival differences between the 2 groups.cBioPortal online software was used to analyze the mutation of ESPL 1.The ESPL 1 protein interaction network was plotted through the STRING database,and its molecular biological functions were analyzed by GO|KEGG enrichment.Results The ESPL 1 expression level of liver cancer tissues was higher than that of paracancerous and normal tissues(0.894±0.643 vs 0.337±0.34,1.908±1.079 vs 0.912±0.77,P<0.05),and the level of ESPL 1 in hepatitis B-related liver cancer was higher than that of non-hepatitis B-related liver cancer(2.159±1.17 vs 1.747±0.983,P<0.05).ESPL 1 expression level was related to gender,age,body mass index(BMI),primary tumor stage,and alpha fetal protein(AFP)level(P<0.05).Primary tumor stage and ESPL 1 expression level were independent risk factors for the prognosis of HCC patients.The expression of ESPL 1 was negatively correlated to the prognosis(HR=1.72,95%CI:1.21-2.41,P<0.05).The mutation rate of ESPL 1 in HCC patients was about 1%,and the prognosis of mutants was poor(P<0.05).The enrichment results show that ESPL 1 was mainly involved in cell cycle,mitosis,chromosome segregation and other biological functions.Conclusion ESPL 1 expression level is upregulated in HCC tissues.It is highly expressed and specific in hepatitis B-related liver cancer.Patients with HCC have high ESPL 1 expression level and ESPL 1 mutations can lead to poor prognosis.ESPL 1 can be used as a potential marker for poor prognosis in patients with HCC.