乙型肝炎病毒相关性慢性肝病中雄激素受体的表达及意义
he expression and significance of androgen receptor in HBV-associated chronic liver diseases
目的：明确AR在HBV相关性慢性肝病中的表达，以及和HCC患者及慢性乙型肝炎病人临床病理学指标的联系，探讨AR在HBV相关致病和致癌中的作用。方法：选取83例HBV相关和14例HBV阴性HCC病例新鲜标本为研究对象、13例肝血管瘤为良性对照；同时选取189例慢性乙型肝炎肝穿刺活检病例作为研究对象、75例病理诊断为"无病理诊断性异常"的病例为阴性对照。荧光定量real-time RT PCR检测mRNA水平的表达；Western blot检测蛋白表达的定量；免疫组化染色En Vision二步法检测蛋白的组织内表达。结果： 在mRNA水平，HBV相关HCC癌旁组织（P=0.000）和癌组织（P=0.000）中AR和HBx表达的相关性具有非常显著性意义；AR（P=0.011）和HBx（P = 0.000）在癌旁组织中的表达均明显高于癌组织的表达；AR在HBV相关HCC癌旁组织（P=0.027）和癌组织（P=0.021）中的表达明显高于HBV阴性HCC。Western blot检测和免疫组织化学染色显示AR和HBx蛋白的表达均与mRNA检测结果相一致。AR在HBV相关HCC癌旁组织中的表达与肝细胞癌的分化程度相关；慢性乙型肝炎患者中，AR的表达和Scheuer评分反应炎症损伤程度的G分级呈负相关（P=0.034）。结论：明确了AR在HBV相关HCC和慢性乙型肝炎肝组织内的表达，结果提示AR在HCC的发生和发展中起了一定作用，HBx诱导AR的表达可能是HBV介导HCC形成中的一种机制。癌旁组织AR的表达高于癌组织，提示雄激素受体治疗在肿瘤形成后可能无效。在慢性乙型肝炎中，AR介导的信号通路可能与炎症反应有关。
Purpose:To explore the AR and HBx expression in both mRNA levels and protein levels, and to find the relationship among them and clinical characteristics. Compared with the negative controls, we tried to find the role of AR in HBV-associated hepatocarcinogenesis. Methods: Eighty-three cases of surgically resected HBV-associated HCC and 14 cases of the HBV-negative HCC were selected. Meanwhile, 13 peritumoral liver tissues from hemangioma served as benign control. One hundred and eighty-nine liver biopsy samples of chronic hepatitis B and 75 cases whose diagnosis as "No pathological diagnostic abnormal" were also selected. The expressions at mRNA levels were detected by fluorescence quantitative real-time RT-PCR. Western blot and En Vision immunohistochemical stain investigated the protein expressions. Results: In 83 HBV-associated HCC cases, in both peritumoral tissues (P=0.000) and tumors (P=0.000), AR mRNA levels correlated positively with HBx; The expression of AR (P=0.011) and HBx (P=0.000) was significantly higher in peritumoral tissues than in tumors; HBV-associated HCC cases had significantly higher AR mRNA than HBV-negative HCC in both peritumoral tissues (P=0.027) and tumors (P=0.021). The results from western blot analysis and Immunohistochemical stain were consistent with those of mRNA levels.In chronic hepatitis B patients, the expression of AR correlated with the grade of Scheuer scores (P=0.034). Conclusions: To clarified the expression of AR in HBV-associated HCC and chronic hepatitis B cases. AR plays a role in HBV-associated hepatocarcinogenesis. HBx-induce AR expression may be a mechanism of hepatocarcinogenesis. AR had stronger expression in peritumoral tissues than in tumors implied that the expression of AR increases during preneoplastic stages and that progression towards cancer development can suppress maintain AR expression levels. It is therefore proposed that androgen therapy may be ineffective after establishment of tumor. In chronic hepatitis B, AR pathway may be related with inflammation.
顾栋桦、朱荣
肿瘤学内科学基础医学
病理学雄激素受体乙型肝炎病毒肝细胞癌慢性乙型肝炎X蛋白
Pathology Androgen receptorHepatitis B virusHepatocellular carcinomaChronic hepatitis Bx gene
顾栋桦,朱荣.乙型肝炎病毒相关性慢性肝病中雄激素受体的表达及意义[EB/OL].(2011-02-01)[2025-08-10].http://www.paper.edu.cn/releasepaper/content/201102-12.点此复制
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