高尔基体糖蛋白73的表达特征及其对肝癌与肝硬化的鉴别诊断价值

Expression profiles and differential diagnostic value of serum Golgi protein-73 in patients with liver cirrhosis and primary hepatic carcinoma

目的研究血清高尔基体蛋白73（GP73）的表达特征及其在肝癌与肝硬化鉴别诊断中的临床价值。方法采用酶联免疫吸附试验（ELISA）检测80例原发性肝癌、65例肝硬化和50名健康体检者血清GP73含量，同时用电化学发光法平行测定血清AFP。多组比较采用Kruskal-Wallis检验，两组比较采用Mann-Whitney检验，ROC曲线分析检测效能并确定其临界值，敏感度、特异度比较用配对χ^2检验，GP73表达与临床参数的关系用Spearman等级相关分析。结果肝癌组GP73浓度中位数为282．0μg／L，高于肝硬化组（211．8μg／L）和健康对照组（58．3μg／L），差异有统计学意义（H=93．30，P〈0．01）。GP73、AFP鉴别肝癌与肝硬化患者的最佳临界值分别为318．1μg／L和13．4μg／L时，GP73的敏感度为45．0%（36／80），低于AFP的65．0％（52／80），χ^2=8．02，P〈0．05;GP73的特异度为83．1％（54／65），低于AFP的87．7％（57／65），χ^2=0．27，P〉0．05；GP73诊断肝癌的ROC曲线下面积为0．65（95％可信区间0．54～0．72），与AFP曲线下面积0．75（95％可信区间0．67～0．83）相比，差异无统计学意义（Z=1．88，P〉0．05）。血清GP73与肝硬化、血管浸润及肿瘤分期相关（r值分别为0．27、0．29、0．27，P值均〈0．05），与性别、年龄、AFP〉13．4μg／L、肿瘤大小和远处转移无相关关系（r值分别为0．13、0．10、0．03、0．18、0．04，P值均〉0．05）。结论在肝癌与肝硬化的鉴别中，血清GP73与AFP的诊断效能相似，但AFP的敏感度优于GP73。血清GP73的过表达可能与肿瘤的负荷和侵袭性有关。

Objective To investigate the expression profiles of serum Golgi protein-73 （GP73） in liver cirrhosis and primary hepatic carcinoma （PHC） and determine its clinical value for differential diagnosis. Methods Serum protein expressions of GP73 and alpha-fetoprotein （AFP） were detected by enzymelinked immunosorbent assay and chemiluminescence assay, respectively, in patients with PHC （n = 80）, liver cirrhosis （n = 65）, and healthy controls （n = 50）. Inter-group changes were assessed by Kruskal-Wallis test, and significance of these differences was assessed by Mann- Whitney test. A receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic efficiency and determine the cut-off values for GP73 and AFP. Sensitivity and specificity were compared by the Chi-squared test. Correlation between serum GP73 expression and clinical parameters was determined by Spearman＇s rank correlation analysis. Results The PHC group showed significantly higher serum GP73 （282.0 μg/L） than the liver cirrhosis group （211.8 μg/L） andcontrol group （58.3 μg/L） （H = 93.30,P 〈 0.01）. For differential diagnosis of PHC and liver cirrhosis, the cut-off value was 318.1 μg/L for GP73 and 13.4 μg/L for AFP. Sensitivity of GP73 was lower than AFP （45% （36/80） vs. 65% （52/80）;χ^2 = 8.02, P 〈 0.05）. Specificity of GP73 was lower than AFP but no significance was found （83.1% （54/65） vs. 87.7% （57/65）;χ^2 = 0.27, P 〉 0.05）. The areas under the ROC curves were not significantly different between GP73 and AFP （0.65 （95% confidence interval （CI）： 0.544）.72） vs. 0.75 （95% CI： 0.67-0.83）; Z = 1.88, P 〉 0.05）. The area under the ROC curves increased but not significantly （0.80 （95% CI： 0.73-0.88） vs. 0.75 （95% CI： 0.67-0.83）; Z = 2.61, P 〉 0.05）. Serum GP73 was correlated with liver cirrhosis （r = 0.27）, vascular invasion （r = 0.29）, and TNM staging （r = 0.27） （aUP〈 0.05）, but not with sex （r = 0.13）, age （r = 0.10）, enhanced AFP （〉 13.4 μg/L; r = 0.03）, tumor size （r = 0.18）, or distant metastasis （r = 0.04）, allP 〈 0.05. Conclusion Serum GP73 and AFP have comparable diagnostic efficiency, but the sensitivity of AFP is superior for differential diagnosis of liver cirrhosis and primary hepatic carcinoma. Elevated serum GP73 may be correlated with liver tumor load and aggressiveness.