高尔基体蛋白73在临床中的异常表达及其在乙型肝炎病毒相关肝细胞癌诊断和预后中的作用
Abnormal Expression of Golgi Protein 73 in Clinical Values and Their Role in HBV-Related Hepatocellular Carcinoma Diagnosis and Prognosis.
作者信息
Sai Wenli, Wang Li, Zheng Wenjie, Yang Junling, Pan Liuhong, Cai Yin, Qiu Liwei, Zhang Haijian, Wu Wei, Yao Dengfu
机构信息
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China.
Medical School, Nantong University, Nantong, China.
出版信息
Hepat Mon. 2015 Dec 29;15(12):e32918. doi: 10.5812/hepatmon.32918. eCollection 2015 Dec.
BACKGROUND
The up-regulation of hepatic Golgi protein 73 (GP73) is associated with the progression of hepatocellular carcinoma (HCC). However, the exact mechanism and clinical values of its diagnosis and prognosis still need to be clarified.
OBJECTIVES
To investigate the clinical values of abnormal liver or circulating GP73 expression and their effect on HCC diagnosis and prognosis.
MATERIALS AND METHODS
The expression of GP73 was investigated in 88 cancerous and self-control non-cancerous tissues using tissue microarrays with immunohisto- chemistry and was confirmed by Western blotting. Circulating GP73 levels were detected in the sera of 281 patients with liver diseases using enzyme-linked immunosorbent assay.
RESULTS
The levels of circulating GP73 expression in the HCC group were higher than those in any group of benign liver diseases or controls. No significant difference was found between GP73 expression and patients' sex or age, tumor size, or AFP level except for those with hepatitis B virus (HBV) infection or distal metastasis (P < 0.05). The area under the receiver operating characteristic curve, sensitivity, and specificity for HCC diagnosis were 0.881, 78.34%, and 77.59% for GP73 levels over 70 μg/L or 0.754, 71.97%, and 84.48% for alpha-fetoprotein levels over 50 μg/L, respectively. The total incidence of GP73 plus alpha-fetoprotein was up to 87.26% for HCC. A positive GP73 result with brown particles was mainly located in the cytosol, with a few in the nucleus and none in the cell membrane, with abnormal expression in HCC tissues (480.7 ± 148.7) that was significantly higher (t = 10.730, P < 0.001) than those in their non-cancerous tissues (208.0 ± 66.1). The high GP73 expression in HCC was related to lymph node metastasis (χ(2) = 6.940, P = 0.008), gross classification (χ(2) = 6.311, P = 0.012), HBV (χ(2) = 4.803, P = 0.028), tumor node metastasis staging (χ(2) = 4.887, P = 0.027), and five-year survival (χ(2) = 5.206, P = 0.023).
CONCLUSIONS
Abnormality of hepatic or circulating GP73 expression should be regarded as an emerging biomarker for HCC diagnosis and prognosis.
背景
肝高尔基体蛋白73（GP73）的上调与肝细胞癌（HCC）的进展相关。然而，其诊断和预后的确切机制及临床价值仍有待阐明。
目的
探讨肝脏或循环中GP73表达异常的临床价值及其对HCC诊断和预后的影响。
材料与方法
采用组织芯片免疫组化法检测88例癌组织及其自身对照的非癌组织中GP73的表达，并通过蛋白质印迹法进行验证。采用酶联免疫吸附测定法检测281例肝病患者血清中循环GP73水平。
结果
HCC组循环GP73表达水平高于任何一组良性肝病或对照组。除乙型肝炎病毒（HBV）感染或远处转移患者外，GP73表达与患者性别、年龄、肿瘤大小或甲胎蛋白水平之间无显著差异（P<0.05）。GP73水平超过70μg/L时，HCC诊断的受试者工作特征曲线下面积、灵敏度和特异性分别为0.881、78.34%和77.59%；甲胎蛋白水平超过50μg/L时，分别为0.754、71.97%和84.48%。GP73联合甲胎蛋白对HCC的总检出率高达87.26%。GP73阳性结果的棕色颗粒主要位于细胞质中，少数位于细胞核中，细胞膜上无表达，HCC组织中异常表达（480.7±148.7）显著高于其非癌组织（208.0±66.1）（t=10.730，P<0.001）。HCC中高GP73表达与淋巴结转移（χ²=6.940，P=0.008）、大体分类（χ²=6.311，P=0.012）、HBV（χ²=4.803，P=0.028）、肿瘤淋巴结转移分期（χ²=4.887，P=0.027）及五年生存率（χ²=5.206，P=0.023）相关。
结论
肝脏或循环中GP73表达异常应被视为HCC诊断和预后的一种新兴生物标志物。
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