17β羟基类固醇脱氢酶13和线粒体融合蛋白2在肝细胞癌组织中的表达变化及生物信息学分析  

Changes in the expression of 17-β-hydroxysteroid dehydrogenase 13 and mitofusin 2 in liver cancer tissue and a bioinformatics analysis

作　　者：曾钗明[1] 严茂林[2] 石益海 郭太林[1] 梅爱农[1] 陈建康[1] 许桂平[1] 何晓红[1] ZENG Chaiming;YAN Maolin;SHI Yihai(Department of Cadre Diagnosis and Treatment, Fujian Provincial Hospital, Fuzhou 350001, China)

机构地区：[1]福建省立医院干部特诊科,福州350001 [2]福建省立医院肝胆外科,福州350001 [3]海军军医大学附属公利医院消化内科,上海200135

出　　处：《临床肝胆病杂志》2019年第12期2736-2740,共5页Journal of Clinical Hepatology

基　　金：福建省自然科学基金(2017J01244);福建省卫计委医学创新课题(2018-CX-8)

摘　　要：目的探索17β羟基类固醇脱氢酶13(HSD17B13)和线粒体融合蛋白2(MFN2)在临床肝细胞癌(以下简称肝癌)组织样本中的表达变化及临床意义;同时采用生物信息学方法,进行目标基因分析。方法选取2017年9月-2018年3月于福建省立医院接受手术治疗的15例肝癌患者,手术后获取肝癌及其周围癌组织进行实验研究。通过实时荧光定量PCR及Western Blot法检测HSD17B13和MFN2基因在肝癌组织和癌旁组织中的表达变化情况,并分析其临床意义。采用单细胞测序数据库、GTEx数据库及TCGA数据库分析HSD17B13和MFN2在肝癌组织中的表达量、肝癌不同分期的表达水平及与肝癌总体生存的关系,并分析二者之间的相关性。符合正态分布的计量资料两组间比较采用t检验,多组间比较采用方差分析;非正态分布的计量资料两组间比较采用Mann-Whitney U检验,多组间比较采用Kruskal-Wallis H检验。采用log-rank检验变量对生存率的影响,Kaplan-Meier法绘制生存曲线。采用Pearson相关分析检验两个变量之间的关系。结果实时荧光定量PCR及Western Blot检测结果显示,相对于癌旁组织,HSD17B13和MFN2基因在肝癌组织中的表达明显下调(PCR检测t值分别为-2.467、-3.933,P值分别为0.020、0.001;Western Blot检测t值分别为-5.357、-5.771,P值分别为0.006、0.026)。生物信息学分析结果表明,肝癌组织中HSD17B13表达明显下调(P<0.05);随着肝癌分期越高,HSD17B13表达水平越低(F=3.220,P=0.023);低HSD17B13表达与不良生存相关(风险比=0.630,P=0.011);在肝癌组织中,MFN2与HSD17B13表达呈显著正相关(r=0.190,P<0.001)。结论MFN2与HSD17B13在肝癌中表达下调,是潜在的具有临床相关性的抑癌基因,可能参与肝癌发生发展过程中的生物学行为,也可成为肝癌筛查、临床分级、预后评估的分子标志物及有效的肝癌治疗靶点。Objective To investigate the change in the expression of 17-β-hydroxysteroid dehydrogenase 13(HSD17B13)and mitofusin 2(MFN2)in hepatocellular carcinoma(HCC)tissue and its clinical significance,and to analyze target genes by bioinformatics methods.Methods Fifteen HCC patients who received surgical treatment in Fujian Provincial Hospital from September 2017 to March 2018 were enrolled.HCC and adjacent tissues were collected after surgery.Real-time PCR and Western blot were used to measure the change in the expression of HSD17B13 and MFN2 in HCC and adjacent tissues,and the clinical significance of such change was analyzed.The single cell sequencing database,the GTEx database,and The Cancer Genome Atlas database were used to analyze the expression of HSD17B13 and MFN2 in HCC tissue and different stages of HCC,as well as its correlation with overall survival of liver cancer.The correlation between the expression of HSD17B13 and MFN2 was also analyzed.For normally distributed continuous data,the t test was used for comparison between two groups,and an analysis of variance was used for comparison between multiple groups;for non-normally distributed continuous data,the Mann-Whitney U test was used for comparison between two groups,and the Kruskal-Wallis H test was used for comparison between multiple groups.The log-rank test was used to investigate the influence of variables on survival rate,and the Kaplan-Meier method was used for plotting the survival curve.A Pearson correlation analysis was used to investigate the relationship between the two variables.Results Real-time PCR and Western blot showed that compared with the adjacent tissue,the HCC tissue had significantly downregulated expression of HSD17B13 and MFN2(PCR:t=-2.467 and-3.933,P=0.020 and 0.001;Western blot:t=-5.357 and-5.771,P=0.006 and 0.026).The bioinformatics analysis showed significantly downregulated expression of HSD17B13 in HCC tissue(P<0.05),and the expression of HSD17B13 decreased with the increase in the stage of HCC(F=3.220,P=0.023);low expressi

关 键 词：癌 肝细胞 孕酮还原酶 线粒体膜转运蛋白质类 基因 肿瘤抑制 计算生物学 

分 类 号：R735.7[医药卫生—肿瘤]