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GP73在原发性肝细胞癌中的高表达及其在经动脉化疗栓塞评估中的作用

High expression of GP73 in primary hepatocellular carcinoma and its function in the assessment of transcatheter arterial chemoembolization.

作者信息

Ai Ning, Liu Wei, Li Zhi-Gang, Ji Hong, Li Bo, Yang Guang

机构信息

Department of Radiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.

Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.

出版信息

Oncol Lett. 2017 Oct;14(4):3953-3958. doi: 10.3892/ol.2017.6697. Epub 2017 Aug 1.

Abstract

Golgi glycoprotein 73 (GP73) is a type II Golgi transmembrane protein and a potential novel marker for the diagnosis of primary hepatocellular carcinoma (PHC). However, its reliability as a serum marker for the diagnosis of PHC following transcatheter arterial chemoembolization (TACE) remains unknown. The aim of the present study was to evaluate the diagnostic value of serum GP73 levels in patients with PHC, to determine its diagnostic accuracy in patients with PHC following TACE. Reverse transcription-quantitative polymerase chain reaction analysis was used to measure GP73 expression in PHC and adjacent para-carcinomatous liver tissue in 40 patients with PHC, and 15 normal liver samples from benign hepatic tumors. The associations between GP73 expression levels with clinicopathological characteristics of the patients were also analyzed. Serum GP73 levels were detected by ELISA in 68 patients with PHC following TACE and 29 healthy individuals. The levels of serum GP73 were tested 2 days prior to intervention, and 7 and 30 days following TACE. GP73 mRNA expression levels in PHC were significantly higher than in the corresponding para-carcinomatous liver and normal liver samples. High expression levels of GP73 mRNA were associated with tumor size, vascular invasion and tumor differentiation, suggesting augmented tumor invasion and metastasis. The expression levels of serum GP73 were markedly higher in the patients with PHC compared with healthy individuals. Serum GP73 levels in the 68 patients with PHC were higher compared with the 29 normal controls [152.5 (76.4-284.5) compared with 49.3 (12.6-26.7) µg/l], and the difference was statistically significant (P<0.01). High levels of serum GP73 were associated with tumor differentiation. The levels of Barcelona clinic liver cancer stage A, B and C were 92.12 (38.9-135.2), 122.9 (55.2-178.5), and 162.55 (110.8-232.9) µg/l, respectively (P<0.05). The serum GP73 levels 7 days following TACE [99.2 (66.7-150.8)] were significantly lower than prior to TACE, and the difference was statistically significant (P<0.05). In the group of 49 patients with serum α-fetoprotein (AFP) levels <400 µg/l, the serum GP73 levels were >132 µg/l. Serum GP73 levels may serve as a potential independent diagnostic marker for PHC, and the combined evaluation of serum GP73 and AFP may increase the diagnostic efficiency of PHC. Significant overexpression of GP73 mRNA was associated with aggressive PHC. However, further research is required to confirm the potential of GP73 as a diagnostic marker.

摘要

高尔基体糖蛋白73(GP73)是一种II型高尔基体跨膜蛋白,是诊断原发性肝细胞癌(PHC)的一种潜在新型标志物。然而,其作为经动脉化疗栓塞术(TACE)后诊断PHC的血清标志物的可靠性仍不清楚。本研究的目的是评估血清GP73水平在PHC患者中的诊断价值,确定其在TACE后PHC患者中的诊断准确性。采用逆转录-定量聚合酶链反应分析来检测40例PHC患者的PHC组织及癌旁肝组织以及15例来自良性肝肿瘤的正常肝组织样本中GP73的表达。还分析了GP73表达水平与患者临床病理特征之间的关联。采用酶联免疫吸附测定法检测68例TACE后的PHC患者和29名健康个体的血清GP73水平。在干预前2天以及TACE后7天和30天检测血清GP73水平。PHC中GP73 mRNA表达水平显著高于相应的癌旁肝组织和正常肝组织样本。GP73 mRNA高表达水平与肿瘤大小、血管侵犯和肿瘤分化相关,提示肿瘤侵袭和转移增强。PHC患者血清GP73表达水平明显高于健康个体。68例PHC患者的血清GP73水平高于29名正常对照者[分别为152.5(76.4 - 284.5)μg/l和49.3(12.6 - 26.7)μg/l],差异具有统计学意义(P<0.01)。血清GP73高水平与肿瘤分化相关。巴塞罗那临床肝癌分期A、B和C期的血清GP73水平分别为92.12(38.9 - 135.2)、122.9(55.2 - 178.5)和162.55(110.8 - 232.9)μg/l(P<0.05)。TACE后7天的血清GP73水平[99.2(66.7 - 150.8)]显著低于TACE前,差异具有统计学意义(P<0.05)。在49例血清甲胎蛋白(AFP)水平<400μg/l的患者组中,血清GP73水平>132μg/l。血清GP73水平可能作为PHC的一种潜在独立诊断标志物,联合评估血清GP73和AFP可能提高PHC的诊断效率。GP73 mRNA的显著过表达与侵袭性PHC相关。然而,需要进一步研究来证实GP73作为诊断标志物的潜力。

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