检测高尔基体蛋白73及其基因表达对原发性肝癌的诊断价值

Value of Detecting Golgi Protein 73 in Plasma and Gene Expression for the Diagnosis of Primary Liver Cancer

目的：探讨高尔基体蛋白73（GP73）血清及其基因表达在原发性肝癌（PHC）中的诊断价值,分析GP73在PHC诊断及高危人群普查的临床意义。方法：采用酶联免疫吸附试验（ELISA）和电化学发光免疫技术定量检测85例PHC、46例肝硬变患者和102名健康人的血清GP73、AFP水平,计算GP73的敏感度、特异度和受试者工作特征曲线（ROC曲线）下面积,采用实时荧光定量（RT-PCR）法检测各组外周血单个核细胞GP73 mRNA的相对表达量,以Ct值比较法计算GP73 mRNA相对表达水平,同时检测12份正常肝组织和12份肝癌组织的GP73 mRNA相对表达水平。结果：PHC组和肝硬变组患者的GP73中位血清质量分数分别为295.6μg/L、213.9μg/L,PHC组GP73中位血清质量分数较肝硬变组明显升高,有显著性差异（P〈0.05）。PHC组和肝硬变组患者的AFP中位血清质量分数分别为9.6μg/L、7.0μg/L,无显著性差异（P〉0.05）。GP73诊断肝癌的敏感度（72.7%）高于AFP（49.8%）,有显著性差异（P〈0.05）,GP73特异度（70.8%）低于AFP（95.9%）,有显著性差异（P〈0.05）。GP73和AFP联合检测肝癌的敏感度为79.6%,特异度为80.3%,ROC曲线下面积为0.840（95%CI为0.770~0.919）;全血GP73 mRNA含量3组间无显著性差异（P〉0.05）,肝癌组织GP73 mRNA表达量（12.87）明显高于正常肝组织（1.08）,有显著性差异（P〈0.05）。结论：GP73诊断PHC具有较好的敏感度,GP73与AFP联合检测可进一步提高诊断早期肝癌的敏感度。全血标本GP73 mRNA检测不能作为诊断原发性肝癌的肿瘤标志,肝组织标本GP73 mRNA可为诊断原发性肝癌的肿瘤标志,但存在创伤大、风险大等弊端。血清GP73联合AFP检测可显著提高PHC诊断,二者联合可用于PHC高危人群的普查及筛选。

Objective： To investigate the value of Golgi protein 73（ GP73） and gene expression in the diagnosis of hepatocellular carcinoma（ PHC）; to analyse the clinical significance of serum GP73 in diagnosis of PHC for screening of high-risk groups. Methods： Took enzyme- linked immunosorbent assay（ ELISA） quantitative detection of serum GP73 and AFP levels in 85 cases of PHC,46 patients with cirrhosis and 102 healthy people. Calculated the sensitivity,specificity,and receiver operating characteristic curve under GP73 area（ area under the ROC curve）,real- time quantitative（ RT- PCR） was used to detect the relative expression of GP73 mRNA in mononuclear cells in peripheral blood in each group,GP73 mRNA relative expression levels were detected with ct value comparison method,simultaneously explored the 12 GP73 mRNA in normal liver tissue and the 12 HCC tissues relative expression levels. Results： Serum concentrations of GP73 median in PHC group and cirrhosis patients were 295. 6 μg / L,213. 9 μg / L. The GP73 median serum concentration difference between the two groups were statistically significant（ P〈0. 05）. The median serum AFP concentrations in patients with PHC and cirrhosis were 9. 6 μg / L,7. 0 μg / L. The serum AFP concentration difference between the two groups were no significant difference（ P〉0. 05）. GP73 diagnostic sensitivity of hepatocellular carcinoma（ 72. 7%） was higher than the AFP（ 49. 8%,P〈0. 05）; GP73 specificity（ 70. 8%） was lower than the AFP（ 95. 9%,P〈0. 05）. GP73 and AFP united detection sensitivity for hepatocellular carcinoma was 79. 6%,specificity 80. 3%; the area under the ROC curve was 0. 849（ 95% CI of 0. 770 ~ 0. 919）; whole blood GP73 mRNA showed no significant difference among the three groups（ P〉0. 05）,GP73 mRNA expression of hepatocellular carcinoma（ 12. 87）was significantly higher than in normal liver tissue（ 1. 08）. Conclusion： GP73 in PHC has better diagnostic sensitivity,GP73 and AFP united detection can further improve the early diagnosis of liver cancer. GP73 mRNA detection in whole blood samples cannot be used as a diagnostic marker of primary liver cancer; liver tissue samples GP73 mRNA can be as tumor markers in the diagnosis of primary liver cancer,but have with trauma and risks. AFP serum GP73 united detection can significantly improve the diagnosis of PHC; their combination can be used to PHC screening in high- risk populations.