羧基末端截短型乙型肝炎病毒X蛋白在肝细胞癌与癌旁组织中的表达及其在术后预后中的作用  

Expression of carboxylic acid-terminal truncated hepatitis B virus X protein in hepatocellular carcinoma and adjacent tissues and its effect on postoperative prognosis

作　　者：钟晓怡 马龙腾 陈曦 吴婷 李楠[2] 曹广文[1] 殷建华 ZHONG Xiao-yi;MA Long-teng;CHEN Xi;WU Ting;LI Nan;CAO Guang-wen;YIN Jian-hua(Department of Epidemiology,Faculty of Naval Medicine,Naval Medical University (Second Military Medical University),Shanghai 200433,China;Department of Hepatic Surgery (Ⅵ),Eastern Hepatobiliary Surgery Hospital,Naval Medical University (Second MilitaryMedical University),Shanghai 200438,China)

机构地区：[1]海军军医大学(第二军医大学)海军医学系流行病学教研室,上海200433 [2]海军军医大学(第二军医大学)东方肝胆外科医院肝外六科,上海200438

出　　处：《第二军医大学学报》2019年第2期125-132,共8页Academic Journal of Second Military Medical University

基　　金：国家重点基础研究发展计划(2015CB554005);国家自然科学基金(81373067;81502882)~~

摘　　要：目的探讨肝细胞癌(HCC)患者肝癌组织和癌旁组织中羧基末端截短型乙型肝炎病毒X蛋白(Ct-HBx)的表达及其与患者术后预后的关系。方法采用免疫组织化学染色法检测462例肝癌组织、配对的263例癌旁组织和配对的25例癌栓组织中Ct-HBx蛋白的表达,分析其与临床病理参数的关系,探讨Ct-HBx蛋白的表达与HCC患者术后预后的关系。结果 Ct-HBx蛋白表达在配对的263例肝癌组织和癌旁组织中阳性率分别为43.73%(115/263)和11.79%(31/263);多因素Cox风险回归模型分析结果显示年龄、门静脉癌栓(PVTT)、术前天冬氨酸转氨酶(AST)、术前甲胎蛋白(AFP)、主瘤旁微小子灶、术前巴塞罗那临床肿瘤(BCLC)分期和术后抗病毒治疗是HCC患者术后复发的独立危险因素(P均<0.05),门静脉癌栓、术前AFP、肿瘤包膜、术前BCLC分期和Ct-HBx蛋白表达是HCC患者术后生存的独立危险因素(P均<0.05)。在263对配对样本中,肝癌组织中Ct-HBx蛋白的表达与性别、糖类抗原19-9(CA19-9)、术后抗病毒治疗有关(P均<0.05)。肝癌组织和癌旁组织中Ct-HBx蛋白均为阴性表达的患者术后3年无瘤生存率高于Ct-HBx蛋白在肝癌组织阴性表达且在癌旁组织阳性表达的患者(P=0.050 1)。结论当HCC患者肝癌组织中Ct-HBx蛋白表达呈阴性时,癌旁组织中Ct-HBx蛋白的表达情况可能与术后预后有关,可作为预测术后肿瘤生存和复发的标志物。Objective To determine the expression of carboxylic acid-terminal truncated hepatitis B virus X protein(Ct-HBx)in hepatocellular carcinoma(HCC)tissues and corresponding adjacent non-tumor tissues,and to explore its effect on postoperative prognosis of HCC patients.Methods Immunohistochemistry was performed to measure the expression levels of Ct-HBx in 462 HCC tissues,263 matched adjacent tissues and 25 matched tumor thrombus tissues.The relationships between Ct-HBx expression and clinicopathological data and postoperative prognosis of HCC patients was analyzed.Results The positive rates of Ct-HBx in 263 HCC and paired adjacent tissues were 43.73%(115/263)and 11.79%(31/263),respectively.Multivariate Cox regression analysis showed that age,portal vein cancer thrombus(PVTT),preoperative aspartate aminotransferase(AST),preoperativeα-fetoprotein(AFP),small daughter nodule,preoperative Barcelona Clinic Liver Cancer(BCLC)stage and postoperative antiviral treatment were independent risk factors of postoperative recurrence of HCC patients(all P<0.05),and the PVTT,preoperative AFP,tumor encapsulation,preoperative BCLC stage and Ct-HBx protein expression were independent risk factors for postoperative survival of HCC patients(all P<0.05).Analysis results of 263 paired HCC and adjacent tissues showed that the expression of Ct-HBx in the HCC tissues was related to gender,carbohydrate antigen 19-9(CA19-9)and postoperative antiviral treatment(all P<0.05).Compared with the patients with negative Ct-HBx in HCC tissues and positive Ct-HBx in adjacent tissues,the patients with negative Ct-HBx in both HCC and adjacent no-tumor tissues had significantly higher 3-year disease free survival rate(P=0.050 1).Conclusion For HCC patients with negative expression of Ct-HBx in HCC tissues,the expression level of Ct-HBx in corresponding adjacent no-tumor tissues is related to the postoperative prognosis of HCC patients,and it may be a potential molecular biomarker to predict postoperative survival and recurrence.

关 键 词：肝肿瘤 肝细胞癌 乙型肝炎病毒 羧基末端截短型乙型肝炎病毒X蛋白 存活率分析 预后 

分 类 号：R735.7[医药卫生—肿瘤]