多巴胺受体1在肝细胞癌中的表达与预后的关系及其对肝癌细胞增殖的影响  

Correlation of the Expression of Dopamine Receptor 1 with Clinicopathological Parameters in Human Hepatocellular Carcinomas and Its Affection on the Proliferation of HepG2 Hepatoma Carcinoma Cell

作　　者：严俨[1,2] 潘家浩[1] 陈东泰[1] 陈泳花 元云飞[3] 曾维安[1] 

机构地区：[1]华南肿瘤学国家重点实验室//中山大学肿瘤防治中心麻醉科,广东广州510060 [2]惠州市中心人民医院,广东惠州516001 [3]华南肿瘤学国家重点实验室//中山大学肿瘤防治中心肝胆科,广东广州510060

出　　处：《中山大学学报（医学科学版）》2015年第6期833-840,共8页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金(30972849)

摘　　要：【目的】通过探讨多巴胺受体1(DRD1)蛋白在肝细胞癌组织的表达,分析其与肝癌患者临床病理因素及预后的关系,初步探讨DRD1的激动剂SKF38393和拮抗剂SCH23390对肝癌细胞株HepG2增殖的影响。【方法】采用免疫组织化学方法检测147例肝细胞癌组织中DRD1蛋白的表达情况,通过统计分析其与临床病理因素和预后的关系,同时使用SKF38393和SCH23390分别作用于肝癌细胞Hep G2,利用细胞增殖实验检测其对细胞增殖率的影响。【结果】在147例肝癌组织中DRD1阳性表达的有89例(60.5%);相关性分析结果显示,DRD1在肝癌中高表达与乙肝表面抗原以及血管侵犯相关(P<0.05)。DRD1蛋白阳性表达的患者无复发生存期(P<0.05)与总生存期(P<0.001)明显较短。Cox多因素分析结果揭示,DRD1表达水平是肝癌患者术后无复发生存期独立危险因素之一(P<0.05),且具有重要的预后预测价值。肝癌细胞Hep G2的细胞增殖实验结果表明SCH23390明显抑制HepG2增殖(P<0.05);SKF38393明显促进HepG2增殖(P<0.05)。【结论】DRD1蛋白在肝细胞癌组织中表达阳性与侵袭转移相关;DRD1可作为预测肝癌患者预后的独立分子标志物;DRD1可能与肝癌细胞的增殖相关。【Objective】 This study aims to investigate the correlation of DRD1 protein expression with clinicopathological characteristics and the prognosis in human hepatocellular carcinomas（HCC）,and investigate the impact on the proliferation of Hep G2 with the agonist SKF38393 and the antagonist SCH23390. 【Methods】 The method of immunohistochemistry was utilized to examine protein expression of DRD1 in 147 cases of HCC tissues. The clinical / prognosis significance of DRD1 expression was statistically analyzed and test the proliferation of Hep G2 by cell proliferation assay after the treatment of SKF38393 and SCH23390. 【Results】High expression of DRD1 was observed in 89 of 147（60.5%） of HCC. Correlation analysis demonstrated that high expression of DRD1 in HCC was significantly correlated with HBs Ag and vascular invasion（P〈0.05）. In addition, DRD1-positive expression was associated with poor recurrence-free survival（RFS）（P〈0.05） and overall survival（OS）（P 〈0.001）. Importantly, DRD1 expression was significant independent factor for RFS in HCC in Cox multivariate analysis（P〈0.05）, and had certain prognostic value. The result of the experiment about the proliferation of Hep G2 indicated that SCH23390 inhibit the proliferation of Hep G2, whileSKF38393 promote the proliferation of Hep G2 apparently（P〈0.05）. 【Conclusion】 The findings provide evidence that intensive expression of DRD1 might be important in the tumor differentiation, invasive and metastasis of HCC, and serve as independent biomarker to predict the HCC prognosis.DRD1 might relate to the proliferation of hepatocellular carcinomas cell.

关 键 词：肝细胞癌 多巴胺受体1 肝癌细胞株HEPG2 COX多因素分析 预后 细胞增殖 

分 类 号：R738.1[医药卫生—肿瘤]