血清中磷酯酰肌醇蛋白聚糖-3及高尔基体蛋白-73异常表达对肝癌的诊断价值
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江苏省卫生厅自然科学基金项目(YG201311);江苏大学临床科技发展基金项目(JLY20120103)


The diagnostic value of serum phosphatidylinositol proteinglycan 3 and Golgi protein 73 in hepatocellular carcinoma
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    摘要:

    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 mRNA及GP73 mRNA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) -滋g/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) -滋g/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9.3 -滋g/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 mRNA和GP73 mRNA相对表达量分别为8.91 ± 3.70-68.41 ± 32.86,肝硬化组GPC3 mRNA和GP73 mRNA相对表达量分别为3.04 ± 0.58-2.32 ± 0.25,肝癌组GPC3 mRNA-GP73 mRNA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 mRNA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mRNA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。

    Abstract:

    Objective:To investigate the diagnostic value of serum and hepatic tissue Golgi protein 73 (GP73) and phosphatidy- linositol proteinglycan 3 (GPC3) in hepatocellular carcinoma (HCC). Methods:The peripheral serum and tissue samples from 70 individuals were collected,including 39 HCC patients and 31 cirrhotic patients. The expression levels of serum GP73 and GPC3 were detected by ELISA;the expression levels of tissue GPC3 mRNA and GP73 mRNA were measured by RT-PCR. The differences of GP73 and GPC3 expression between liver cancer group and cirrhosis group were observed. The correlation between GP73 and GPC3 expression and clinical stage of HCC was analyzed,and the correlation between GP73 and GPC3 expression and pathological grade of HCC was also analyzed. Results:The expression level of serum GP73 and GPC3 from the HCC patients was significantly higher than those from the cirrhotic group (P < 0.001). The GPC3 value for the cutting off was 9.3 μg/L,the sensitivity was 89.74%,the specificity was 96.77%,the positive predictive value was 97.20%,and the negative predictive value was 88.20%. The GP73 value for the cutting off was 77.68 ng/ml,the sensitivity was 92.31%,the specificity was 83.87%,the positive predictive value was 87.80%,and the negative predictive value was 89.70%. The expression levels of GP73 and GPC3 in HCC patients show no statistic difference between age,gender,tumor size and clinical stage;nevertheless,the expression level of GPC3 in HCC patients seemed to be correlated with tumor pathological grade. Conclusion:Over expression of liver GPC3 and GP73 were associated with HCC,and quantitative detection of serum GPC3 and GP73,which were more sensitive than AFP,should be a useful marker for diagnosis of HCC.

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曹风华,汪顺才,马 洁,朱梦琪,马久明,周 华,虞腊青,陈明泉,经继生.血清中磷酯酰肌醇蛋白聚糖-3及高尔基体蛋白-73异常表达对肝癌的诊断价值[J].南京医科大学学报(自然科学版),2015,(3):393-397

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  • 收稿日期:2014-12-09
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  • 在线发布日期: 2015-03-10
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