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目的 :探究肝组织及外周血磷酯酰肌醇蛋白聚糖-3(phosphatidylinositol proteinglycan 3,GPC3)及高尔基体糖蛋白-73(Golgi protein 73,GP73)高表达对肝癌的诊断价值。方法 :用ELISA法检测39例肝癌患者及31例肝硬化患者外周血GPC3及GP73浓度,RT-PCR法检测两组患者肝组织中GPC3 m RNA及GP73 m RNA表达水平,比较研究肝癌及肝硬化患者外周血、肝组织中GPC3及GP73的表达差异,分层分析此两种蛋白表达与肝癌不同临床分期、病理分级的相关性。结果:肝癌组外周血GPC3、GP73浓度分别为(16.81±0.56)μg/L、(115.92±7.01)ng/ml,肝硬化组外周血GPC3、GP73浓度分别为(7.41±0.25)μg/L、(64.63±3.07)ng/ml,肝癌组外周血GPC3、GP73浓度均显著高于肝硬化组(P<0.001)。GPC3值为9.3μg/L时诊断肝癌的灵敏度和特异度分别为89.74%和96.77%,阳性预测值97.20%,阴性预测值88.20%;GP73截断值为77.68 ng/ml时,其诊断肝癌的灵敏度92.31%,特异度83.87%,阳性预测值87.80%,阴性预测值89.70%。肝癌组GPC3 m RNA和GP73 m RNA相对表达量分别为8.91±3.70、68.41±32.86,肝硬化组GPC3 m RNA和GP73 m RNA相对表达量分别为3.04±0.58、2.32±0.25,肝癌组GPC3 m RNA、GP73 m RNA表达均高于肝硬化组(P均<0.05)。上述结果可知肝癌患者癌组织GPC3、GP73 m RNA表达水平与外周血相应蛋白浓度一致。肝癌患者中外周血GP73、GPC3蛋白浓度及组织m RNA表达水平与年龄、性别、肿瘤大小及肝癌临床分期间无统计学意义;而肝癌患者GPC3表达与病理分级间存在统计学差异,病理分级为3级的肝癌患者GPC3表达水平低于1~2级患者。结论:GP73、GPC3在肝癌患者中表达明显增高,且灵敏度高于AFP,而特异度与其相当,有望成为一种新的、较好早期诊断HCC的血清标志物;另外,GPC3表达对肝癌细胞的分化程度有一定的指示作用。
Objective: To investigate the diagnostic value of high expression of phosphatidylinositol proteintecan 3 (GPC3) and Golgi protein 73 (GP73) in liver tissue and peripheral blood on the diagnosis of liver cancer. Methods: The concentrations of GPC3 and GP73 in peripheral blood of 39 patients with hepatocellular carcinoma and 31 patients with cirrhosis were determined by ELISA. The expression of GPC3 m RNA and GP73 mRNA in liver tissue were detected by RT-PCR. The expression of GPC3 and GP73 in peripheral blood and liver of patients were analyzed by stratified analysis of the correlation between the expression of these two proteins and clinical stages and pathological grade of HCC. Results: The levels of GPC3 and GP73 in peripheral blood of hepatocellular carcinoma patients were (16.81 ± 0.56) μg / L and (115.92 ± 7.01) ng / ml, respectively. The levels of GPC3 and GP73 in liver cirrhosis patients were (7.41 ± 0.25) μg / (64.63 ± 3.07) ng / ml, respectively. The levels of GPC3 and GP73 in liver cancer group were significantly higher than those in cirrhosis group (P <0.001). The sensitivity and specificity of the diagnosis of liver cancer with GPC3 value of 9.3μg / L were 89.74% and 96.77%, respectively, the positive predictive value was 97.20% and the negative predictive value was 88.20%, while the sensitivity and specificity of GP73 was 77.68ng / ml 92.31%, specificity 83.87%, positive predictive value 87.80%, negative predictive value 89.70%. The relative expression levels of GPC3 m RNA and GP73 m RNA in hepatocellular carcinoma were 8.91 ± 3.70,68.41 ± 32.86, respectively. The relative expression levels of GPC3 m RNA and GP73 m RNA in cirrhosis were 3.04 ± 0.58 and 2.32 ± 0.25, , GP73 m RNA expression were higher than the cirrhosis group (P all <0.05). The above results show that the expression levels of GPC3 and GP73 mRNA in cancer tissues of HCC patients are consistent with the corresponding protein concentrations in peripheral blood. The levels of GP73, GPC3 protein and tissue m RNA in peripheral blood of HCC patients were not significantly different from those of age, gender, tumor size and clinical stage of HCC. However, the expression of GPC3 in HCC patients was significantly different from that of pathological grade Grade 3 liver cancer patients with GPC3 expression levels lower than 1 to 2 patients. Conclusion: The expression of GP73 and GPC3 in hepatocellular carcinoma patients was significantly higher than that in AFP patients, but the sensitivity was higher than that in AFP patients. The specificity of GPC3 and GPC3 was expected to be a new serum marker for early diagnosis of HCC. In addition, Degree of differentiation has a certain indicator.