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良性肝病进展为癌前病变和肝细胞癌过程中高尔基糖蛋白 73 的表达逐渐增加,与患者的预后相关。

Gradually increased Golgi protein 73 expression in the progression of benign liver diseases to precancerous lesions and hepatocellular carcinoma correlates with prognosis of patients.

机构信息

Third Central Clinical College of Tianjin Medical University, Tianjin, China; Department of Hepatobiliary Surgery, Third Central Hospital of Tianjin, Tianjin, China.

出版信息

Hepatol Res. 2013 Nov;43(11):1199-210. doi: 10.1111/hepr.12078. Epub 2013 May 10.

Abstract

AIM

Serum Golgi protein 73 (sGP73) is a novel biomarker for hepatocellular carcinoma (HCC). However, there are few reports on the pattern of GP73 expression in the progression of benign liver diseases to precancerous lesions and HCC. This study aimed to investigate GP73 expression and its correlation with clinicopathological parameters.

METHODS

Tissue GP73 (tGP73) levels were detected in specimens of group A (n = 186) including HCC, peritumoral tissue (PTL), high/low-grade hepatic atypical hyperplasia (AH), chronic hepatitis B (CHB) and normal controls (NC) by immunohistochemistry, and GP73 expression in group B (n = 159) and group C (n = 16) were detected by reverse transcription polymerase chain reaction and western blot, respectively. sGP73 levels were detected in subjects of group D (n = 287) by enzyme-linked immunoassay.

RESULTS

GP73 expression increased gradually from NC, CHB, PTL to high-grade AH and HCC at both protein and mRNA levels (P < 0.05), while sGP73 in the HCC group was lower than in the liver cirrhosis (LC) group (P < 0.001). Both tGP73 and sGP73 levels were negatively associated with tumor size and tumor-node-metastasis stage, and tGP73 levels were positively associated with tumor differentiation. The high-tGP73 group showed significantly better overall and disease-free survival than the low-tGP73 group (P = 0.008, P = 0.018). Multivariate analysis revealed that the tGP73 level was an independent prognostic factor for HCC, but not sGP73.

CONCLUSION

GP73 expression pattern suggests that the regulatory mechanism of GP73 is related to the progression of chronic liver diseases. Furthermore, a high level of tGP73 is a favorable prognostic factor for HCC.

摘要

目的

高尔基体蛋白 73(sGP73)是肝细胞癌(HCC)的一种新型生物标志物。然而,关于 GP73 表达在良性肝病进展为癌前病变和 HCC 中的模式的报道较少。本研究旨在探讨 GP73 表达及其与临床病理参数的关系。

方法

采用免疫组织化学法检测 A 组(n=186)包括 HCC、癌旁组织(PTL)、高低级别肝非典型增生(AH)、慢性乙型肝炎(CHB)和正常对照组(NC)的组织 GP73(tGP73)水平,B 组(n=159)和 C 组(n=16)分别采用逆转录聚合酶链反应和 Western blot 检测 GP73 表达,D 组(n=287)采用酶联免疫吸附试验检测 sGP73 水平。

结果

GP73 蛋白和 mRNA 水平均从 NC、CHB、PTL 逐渐升高至高级 AH 和 HCC(P<0.05),而 HCC 组的 sGP73 水平低于肝硬化(LC)组(P<0.001)。tGP73 和 sGP73 水平均与肿瘤大小和肿瘤-淋巴结-转移分期呈负相关,与肿瘤分化呈正相关。高 tGP73 组的总生存期和无病生存期明显优于低 tGP73 组(P=0.008,P=0.018)。多因素分析显示,tGP73 水平是 HCC 的独立预后因素,但 sGP73 不是。

结论

GP73 表达模式表明 GP73 的调控机制与慢性肝病的进展有关。此外,高 tGP73 水平是 HCC 的有利预后因素。

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