高迁移率族蛋白B3异常与肝细胞肝癌患者预后分析  

Clinical significance of high mobility group box-3 abnormality in evaluation of hepatocellular carcinoma prognosis

作　　者：郑文杰 姚敏 巫梦娜 孙建英 方淼 姚登福 ZHENG Wen-jie;YAO Min;WU Meng-na;SUN Jian-ying;FANG Miao;YAO Deng-fu(Research Center of Clinical Medicine,Affiliated Hospital of Nantong University,Nantong 226001,P.R.China;Medicine School of Nantong University,Nantong 226001,P.R.China)

机构地区：[1]南通大学附属医院临床医学研究中心 [2]南通大学医学院免疫教研室 [3]南通大学医学院肿瘤中心

出　　处：《中华肿瘤防治杂志》2020年第1期19-26,共8页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金（81673241;81702419;31872738）;江苏省研究生科研创新计划（KYCX17_1934）;南通市科技项目(MS12017014-4)

摘　　要：目的高迁移率超蛋白家族与肝细胞性肝癌(hepatocellular carcinoma,HCC)发生发展有关,本研究旨在探讨新标志物高迁移率超蛋白家族成员B3(high mobility group Box 3,HMGB3)对肝癌患者预后的临床预测价值。方法以自身配对法收集2015-08-06-2017-05-23南通大学附属医院行手术治疗肝癌患者的肝癌组织和癌旁组织50例,以免疫组化法分析HMGB3蛋白表达,结合癌症基因组图谱(the cancer genome atlas,TCGA)及基因表达数据库相关信息,分析HMGB3基因转录对肝癌患者预后的影响;设计、筛选和验证HMGB3特异shRNA,转染肝癌HCCLM3细胞株,以四甲基偶氮唑盐比色法、克隆形成实验、划痕和Transwell实验分析癌细胞增殖、克隆形成、迁移和侵袭等,分析HMGB3与HCC生物学特性的关系。结果肝癌HMGB3阳性率(72.0%)高于癌旁组织(28.0%),χ2=19.360,P<0.001。TCGA数据库信息显示,372例肝癌组织HMGB3mRNA高于50例正常肝组织,t=5.041,P<0.001;HMGB3高表达患者中位生存期(47.4个月)低于低表达患者(100.6个月),P=0.031;HMGB3高表达的早期肝癌患者中位生存期(71.0个月)低于低表达患者(108.6个月),P=0.033;接受索拉菲尼治疗的HMGB3高表达肝癌患者中位生存期(22.0个月)低于低表达患者(52.0个月),P<0.001;以有效的shRNA-1干扰质粒转染HCCLM3细胞后,癌细胞增殖、克隆形成(t=5.056,P<0.001)、迁移(t=7.4,P<0.001)和侵袭(t=12.2,P<0.001)等生物学行为受抑制,差异均有统计学意义。结论 HMGB3异常表达与肝癌增殖、迁移、浸润和预后密切相关,是肝癌预后判别且具有应用前景的潜在标志物。OBJECTIVE High mobility group box family has been associated with the development and progression of hepatocellular carcinoma(HCC).This study aimed to explore the clinical predictive value of high mobility group Box 3(HMGB3),a new marker of high mobility superprotein family,for the prognosis of HCC patients.METHODS The expression of HMGB3 was analyzed in 50 pairs of HCC tissues and their para-cancerous tissues with immunochemistry from August 6 th,2015 to May 23 rd,2017 at Affiliated Hospital of Nantong University.HMGB3 mRNA in HCC and controls were extracted from the bioinformatic TCGA or GEO databases.Specific shRNAs were transfected into HCCLM3 cells and screened by Western blotting and RT-qPCR.The effects of HMGB3 gene transcription on HCC cells were evaluated by the MTT,colony formation,wound healing and Transwell assay for HCC target value.RESULTS The incidence of HMGB3 expression in HCC tissues(72.0%)was significantly higher than that of their para-cancerous tissues(28.0%),χ2=19.360,P<0.001.Based on the analyses in TCGA,the expression of HMGB3 mRNA in 372 HCC tissues was significantly higher than that in 50 control liver tissues,t=5.041,P<0.001.The median survival time of patients with high expression of HMGB3(47.4 months)was lower than that of patients with low expression(100.6 months),P=0.031.The median survival time of patients with high expression of HMGB3(71.0 months)was lower than that of patients with low expression(108.6 months),P=0.033.The median survival time(22.0 months)of patients with high expression of HMGB3 treated with sorafenib was lower than that of patients with low expression of HMGB3(52.0 months),P<0.001.Moreover,the most effective shRNA-1 plasmid was screened and then transfected into HCCLM3 cells.The capacities of proliferation,colony formation(t=5.056,P<0.001),migration(t=7.4,P<0.001)and invasion(t=12.2,P<0.001)in HCCLM3 cells were significantly inhibited.CONCLUSION Abnormal expression of HMGB3 is closely related to invasion,migration and prognosis of HCC and it could be served as

关 键 词：肝细胞性癌 高迁移率蛋白超家族成员B3 预后 生物学特性 

分 类 号：R735.7[医药卫生—肿瘤]