Golgi Phosphoprotein 2 (GOLPH2) Expression in Liver Tumors and Its Value as a Serum Marker in Hepatocellular Carcinomas
Golgi Phosphoprotein 2 (GOLPH2) Expression in Liver Tumors and Its Value as a Serum Marker in Hepatocellular Carcinomas
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DOI：
10.1002/hep.22843
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发表时间：
2009-05-01
期刊：
影响因子：
13.5
通讯作者：
Kristiansen, Glen
中科院分区：
文献类型：
--
作者：
Riener, Marc-Oliver;Stenner, Frank;Kristiansen, Glen
肝细胞癌（HCC）和胆管癌（BDC）预后不良。因此，监测策略，包括敏感和特异性的血清标志物，早期发现是必要的。最近，高尔基体磷蛋白2（GOLPH 2）已被提议作为HCC的血清标志物，但GOLPH 2在肝组织中的表达数据不可用。我们使用组织芯片和免疫组织化学技术，半定量分析了GOLPH 2蛋白在HCC（n = 170）、良性肝肿瘤（n = 22）、BDC（n = 114）和正常肝组织（n = 105）中的表达。采用双抗体夹心酶联免疫吸附试验（ELISA）检测62例原发性肝癌（HCC）、29例丙型肝炎病毒（HCV）、10例胆管癌（BDC）和12例健康对照者血清GOLPH 2水平。通过免疫组化，121/170（71%）HCC显示GOLPH 2强表达，这与较高的肿瘤分级显著相关（P = 0.01）。97/114（85%）例BDC显示GOLPH 2强表达，GOLPH 2被证明是总生存的独立预后因素（P < 0.05）。与健康对照组（中位数4 mg/L）相比，通过ELISA测量的GOLPH 2血清水平在具有潜在HCV感染的HCC患者（中位数18 mg/L，P < 0.05）和具有BDC的患者（中位数= 14.5 mg/L，P < 0.01）中显著升高。结论：GOLPH 2蛋白在HCC和BDC组织中呈高表达。GOLPH 2蛋白水平可通过EUSA在血清中检测和定量。在丙型肝炎患者中，在疾病过程中的系列ELISA测量似乎是一个有前途的补充血清标志物，在肝癌的监测。GOLPH 2作为血清肿瘤标志物在BDC中的应用值得进一步研究。（《肝脏学》2009年;49：1602-1609）
Hepatocellular carcinomas (HCCs) and bile duct carcinomas (BDCs) have a poor prognosis. Therefore, surveillance strategies including sensitive and specific serum markers for early detection are needed. Recently, Golgi Phosphoprotein 2 (GOLPH2) has been proposed as a serum marker for HCC but GOLPH2 expression data in liver tissues was not available. Using tissue microarrays and immunohistochemistry, we semiquantitatively analyzed GOLPH2 protein expression in patients with HCC (n = 170), benign liver tumors (n = 22), BDC (n = 114) and normal liver tissue (n = 105). A newly designed sandwich enzyme-linked immunoassay (ELISA) was used to analyze GOLPH2 levels in the sera of patients with HCC (n = 62), hepatitis C virus (HCV) (n = 29), BDC (n = 10), and healthy control persons (n = 12). By immunohistochemistry 121/170 (71%) of HCC showed strong GOLPH2 expression, which was significantly associated with a higher tumor grade (P = 0.01). A total of 97/114 (85%) BDCs showed a strong GOLPH2 expression which proved to be an independent prognostic factor for overall survival (P < 0.05). Serum levels of GOLPH2 measured by ELISA were significantly elevated in patients with HCC with underlying HCV infection (median 18 mg/L, P < 0.05) and patients with BDC (median = 14.5 mg/L, P < 0.01) in comparison to healthy controls (median 4 mg/L). Conclusion: GOLPH2 protein is highly expressed in tissues of HCC and BDC. GOLPH2 protein levels are detectable and quantifiable in sera by EUSA. In patients with hepatitis C, serial ELISA measurements in the course of the disease appear to be a promising complementary serum marker in the surveillance of HCC. GOLPH2 should be further evaluated as a serum tumor marker in BDC on a larger scale. (HEPATOLOGY 2009;49:1602-1609.)