GP73联合其他肿瘤标志物检测对AFP阴性原发性肝细胞癌临床诊断价值

Significance of Combined Tests of Serum Golgi Glycoprotein 73 and Other Biomarkers in Diagnosis of Small Primary Hepatocellular Carcinoma

目的早期原发性肝细胞癌患者中80%患者的AFP肿瘤标志物检测结果为阴性,本研究探讨对于AFP阴性的原发性肝细胞癌患者采用联合检查血清高尔基体糖蛋白73(GP73)、扁豆凝集素结合型甲胎蛋白异质体(AFP-L3)、磷脂酰肌醇蛋白聚糖3(GPC3)、脱-γ-羧基凝血酶原(DCP)、CA19-9、铁蛋白(FER)以及癌胚抗原(CEA)的临床意义。方法选取50例原发性肝细胞癌患者(A组)、60例消化系统异常的非原发性肝细胞癌患者(B组)和40例健康人群(C组)纳入本研究。采用酶联免疫分析方法测定血清中GP73、GPC3和DCP含量,采用微量离心柱分离血清AFP-L3,采用电化学发光免疫分析检测血清CA19-9、FER、CEA、AFP-L3以及总AFP,计算AFP-L3所占比例(AFP-L3/总AFP)。结果三组中除FER以外的各项指标差异均极显著(P<0.01),原发性肝细胞癌组患者的7种肿瘤标志物的阳性率均显著高于其他两组(P<0.01),各单项检测中,GP73的灵敏度、准确度以及ROC曲线面积最大,分别为72.0%、86.7%和0.826,GPC3的检测特异性最高为98.0%。结合7种肿瘤标志物检测的临床敏感性、特异性、准确性和ROC曲线面积分别为82.0%、95.0%、90.1%和0.884。结论 GP73和AFP-L3是AFP阴性原发性肝细胞癌患者临床诊断的首选肿瘤标志物,临床上采用多种肿瘤标志物检测能显著提高诊断准确率。

Objective The most commonly used biomarker AFP is negative in 80% patients with small tumor in the early stage of primary hepatocellular carcinoma（ PHC）. To investigate the significance of combined tests of serum golgi glycoprotein 73（ GP73）,lens culinarisagglutininreactive alpha-fetoprotein（ AFP-L3）,glypican 3（ GPC3）,des-gamma-carboxyprothrombin（ DCP）,CA19-9,ferritin（ FER） and carcinoembryonic antigen（ CEA）in diagnosis of small PHC with negative AFP. Methods A total of 50 cases of small PHC,60 cases of non-PHC digestive system disorders and 40 cases of healthy controls were collected. Serum GP73,GPC3 and DCP were analyzed by enzyme-1inked immunosorbent assay（ ELISA）. AFP-L3 was separated by microspincolumn; the levels of CA19-9,FER,CEA,AFP-L3 and total AFP were quantified by electrochemiluminescence immunoassays; percentage of AFP-L3 to total AFP was calculated. Results Levels of all of these biomarkers except FER were significantly different among three groups（ P〈0. 01）. Positive detection rates of seven biomarkers in PHC were higher than other groups（ P〈0. 01）. In individual detection,the highest sensitivity,accuracy rate and area under ROC curve were 72. 0%,86. 7% and 0. 826 by GP73. The biomarker with the highest specificity was GPC3,98. 0%. In combined detection with these seven biomarkers,the sensitivity,specificity,accuracy rate and area under ROC curve were 82. 0%,95. 0%,90. 1% and 0. 884. Conclusion GP73 and AFP-L3 are the better biomarkers to aid the diagnosis of small PHC with negative AFP. The combined detection of biomarkers might improvethe accuracy in diagnosis of small primary hepatocellular carcinoma.