甲胎蛋白低中浓度肝细胞癌AFP-L3和Hsp90α联合检测临床意义

Clinical significance of AFP-L3,Hsp90α test in the diagnosis of hepatocellular carcinoma with low and medium concentration of AFP

目的甲胎蛋白(alpha fetoprotein,AFP)在其低中浓度肝细胞癌(hepatocellular carcinoma,HCC)诊断中有一定局限性,本研究通过对血清甲胎蛋白异质体L3(α-fetoprotein variants-L3,AFP-L3)和热休克蛋白90α(heat shock protein 90α,Hsp90α)的检测,探讨两者在AFP低中浓度HCC诊断中的价值。方法选择2016-02-01-2018-04-30在四川省人民医院诊治的血清AFP为低中浓度(20-400ng/mL)的HCC患者102例,良性肝病患者113例以及健康对照者150名。通过化学发光法检测总AFP和AFP-L3浓度,计算AFP-L3(%)即AFP-L3占总AFP的百分比;用酶联免疫法检测Hsp90α浓度。通过Logistic回归分析和受试者工作特征曲线等方法,比较各指标对HCC的诊断价值。结果HCC组AFP-L3(%)为14.27%,高于良性肝病组(5.05%)和健康对照组(1.20%),H值分别为85.03和155.79,均P<0.001;HCC组Hsp90α浓度为145.19ng/mL,高于良性肝病组(81.31ng/mL)和健康对照组(20.77ng/mL),H值分别为49.40和138.48,均P<0.001;良性肝病组AFP-L3(%)和Hsp90α浓度高于健康对照组,H值分别为128.00和132.53,均P<0.001。单项中AFP-L3(%)的特异性(0.982)高于Hsp90α(0.673),P<0.001;AFP-L3(%)的阳性预测值(0.973)高于Hsp90α(0.681),P<0.001;AFP-L3(%)的诊断符合率(0.851)高于Hsp90α(0.721),P=0.023;AFP-L3(%)的曲线下面积(area under curve,AUC)为0.864,高于Hsp90α(0.778),P=0.048;AFP-L3(%)的灵敏度(0.706)低于Hsp90α(0.775),P=0.009。联检的灵敏度、阴性预测值、诊断符合率和AUC分别为0.941,0.944,0.921和0.962,较单项指标均有提高,均P<0.05。结论AFP-L3(%)和Hsp90α均可作为HCC的肿瘤标志物,两者联检可明显提高AFP低中浓度HCC诊断的灵敏度、诊断符合率和准确度。

OBJECTIVE Alpha fetoprotein(AFP)has some limitations in the diagnosis of hepatocellular carcinoma(HCC)with low and medium levels of AFP.The aim of this study was to investigate the value of serum AFP-L3 and heat shock protein 90α(Hsp90α)in the diagnosis of HCC exhibiting low and medium levels of AFP(20-400 ng/mL).METHODS Totally 102 cases of HCC with low and medium levels of AFP,113 cases of benign liver diseases and 150 cases of healthy controls were collected.Levels of AFP-L3 and AFP were quantified by chemiluminescent immunoassay.Percentages of AFP-L3 in total AFP were calculated.The levels of Hsp90αwere analyzed by enzyme-linked immunosorbent assay.AFP-L3(%)and the levels of Hsp90αin each group were compared and the value of them in the diagnosis of HCC was evaluated using logistic regression and receiver operating characteristic curve.RESULTS AFP-L3(%)in patients with HCC(14.27%)were higher than those in patients with benign liver diseases(5.05%)and healthy controls(1.20%),H values were 85.03 and 155.79,all P<0.001.Levels of Hsp90αin HCC patients(145.19 ng/mL)were higher than those in benign liver diseases patients(81.31 ng/mL)and healthy controls(20.77 ng/mL),H values were 49.40 and 138.48,all P<0.001.AFP-L3(%)and levels of Hsp90αin benign liver diseases patients were higher than those in healthy controls,H values were 128.00 and 132.53,all P<0.001.The specificity(0.982)of AFP-L3(%)was higher than that of Hsp90 a(0.673),P<0.001,the positive predictive value(0.973)of AFP-L3(%)was higher than that of Hsp90α(0.681),P<0.001,the diagnostic coincidence rate(0.851)of AFP-L3(%)was higher than that of Hsp90α(0.721),P=0.023,the area under curve(AUC)of AFP-L3(%)was 0.864,higher than that of Hsp90α(0.778),P=0.048.The sensitivity of 0 AFP-L3(%)is 0.706 lower than that of Hsp90α(0.775),P=0.009.The sensitivity(0.941),negative predictive value(0.944),accordance rate(0.921)and AUC(0.962)of the combined detection were higher than AFP-L3(%)or Hsp90αalone,all P<0.05.CONCLUSIONS AFP-L3(%)and Hsp90αcan be used as diagnostic markers of HCC.The combined detection can improve the sensitivity,accordance rate and accuracy of diagnosis of HCC exhibiting low and medium levels of AFP.