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  • 钟晓怡,马龙腾,陈曦,吴婷,李楠,曹广文,殷建华.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[J].第二军医大学学报,2019,40(2):125-132    [点击复制]
  • ZHONG Xiao-yi,MA Long-teng,CHEN Xi,WU Ting,LI Nan,CAO Guang-wen,YIN Jian-hua.Expression of carboxylic acid-terminal truncated hepatitis B virus X protein in hepatocellular carcinoma and adjacent tissues and its effect on postoperative prognosis[J].Acad J Sec Mil Med Univ,2019,40(2):125-132   [点击复制]
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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
钟晓怡1△,马龙腾1△,陈曦1,吴婷1,李楠2,曹广文1,殷建华1*
0
(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
共同第一作者
*通信作者)
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。
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
DOI:10.16781/j.0258-879x.2019.02.0125
投稿时间:2018-11-14修订日期:2019-01-27
基金项目:国家重点基础研究发展计划(2015CB554005),国家自然科学基金(81373067,81502882).
Expression of carboxylic acid-terminal truncated hepatitis B virus X protein in hepatocellular carcinoma and adjacent tissues and its effect on postoperative prognosis
ZHONG Xiao-yi1△,MA Long-teng1△,CHEN Xi1,WU Ting1,LI Nan2,CAO Guang-wen1,YIN Jian-hua1*
(1. Department of Epidemiology, Faculty of Naval Medicine, Naval Medical University(Second Military Medical University), Shanghai 200433, China;
2. Department of Hepatic Surgery(Ⅵ), Eastern Hepatobiliary Surgery Hospital, Naval Medical University(Second Military Medical University), Shanghai 200438, China
Co-first authors.
* Corresponding author)
Abstract:
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), preoperative α-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.
Key words:  liver neoplasms  hepatocellular carcinoma  hepatitis B virus  carboxylic acid-terminal truncated hepatitis B virus X protein  survival analysis  prognosis