血清5项肿瘤标志物检测对肝癌的临床应用价值

Clinical application value of the detection of five serum tumor markers in primary hepatocellular carcinoma

目的探讨血清甲胎蛋白(AFP)、甲胎蛋白异质体(AFP-L3)、甲胎蛋白异质体比率(AFP-L3%)、异常凝血酶原(DCP)、高尔基体蛋白73(GP73)单项及联合检测在慢性肝病、肝硬化和肝癌中的临床应用价值。方法回顾性分析2019年10月至2020年12月吉林大学第一医院就诊的6202例住院及门诊患者。采用磁微粒化学发光免疫分析法检测各患者上述5项指标。分别将肝癌治疗前及治疗后未缓解组、肝癌治疗后缓解组与慢性肝病及肝硬化组检测结果进行两独立样本的秩和检验分析。通过ROC曲线及Logistic回归评估5项指标单项及联合检测在肝癌治疗前及治疗后未缓解组中的诊断效能及关联程度。对5项指标单项及联合检验阳性率以及诊断肝癌的方法学进行评价。结果肝癌治疗前及治疗后未缓解组、肝癌治疗后缓解组该5项指标与慢性肝病及肝硬化组比较的差异均有统计学意义(P均<0.05)。5项指标诊断肝癌治疗前及治疗后未缓解组的ROC曲线下面积(AUCROC)为0.800~0.914,cut-off值分别为:AFP 7.72 ng/mL,AFP-L30.60 ng/mL,AFP-L3%5.0%,DCP 36.79 ng/mL,GP7378.97 ng/mL;敏感性69.04%~82.94%,特异性78.34%~98.22%,约登指数0.476~0.812。联合检测诊断肝癌治疗前及治疗后未缓解组的AUCROC为0.928~0.996,敏感性83.20%~97.67%,特异性94.89%~98.12%,约登指数0.811~0.955。单项检测阳性率分别为:慢性肝病及肝硬化组0.63%(AFP-L3%)~6.37%(AFP),肝癌治疗前及治疗后未缓解组32.06%(GP73)~79.77%(AFP),肝癌治疗后缓解组5.77%(AFP-L3%)~17.63%(DCP);联合检验阳性率分别为:慢性肝病及肝硬化组3.67%(AFP-L3%+GP73)~11.82%(5项联合),肝癌治疗前及治疗后未缓解组85.80%(AFP+AFP-L3%)~99.82%(5项联合),肝癌治疗后缓解组12.67%(AFP+AFP-L3%)~32.94%(5项联合)。诊断肝癌的敏感性分别为22.62%(GP73)~69.77%(5项联合),特异性分别为88.18%(5项联合)~99.37%(AFP-L3%),总正确率47.44%(GP73)~75.93%(5项联合),阳性预测值92.16%(5项联合)~99.33%(AFP-L3%),阴性预测值38.59%(GP73)~59.43%(5项联合)。结论慢性肝病、肝硬化及肝癌治疗前后5项血清学指标发生不同程度改变,联合检测对原发性肝癌的辅助诊断和评价疗效具有重要的临床应用价值。

Objective To investigate the diagnostic value of single and combined detection of serum alpha-fetoprotein(AFP),alpha-fetoprotein L3(AFP-L3),alpha-fetoprotein L3%(AFP-L3%),des-gamma-carboxyprothrombin(DCP)and golgi protein 73(GP73)in chronic hepatopathy,hepatocirrhosis and hepatocellular carcinoma(HCC).Methods The detection results of serum AFP,AFP-L3,AFP-L3%,DCP and GP73 from 6202 inpatients and outpatients in the First Hospital of Jilin University during October 2019 and December 2020 were analyzed retrospectively.The five tumor markers were detected by the magnetic particle chemiluminescence immunoassay.The detection results of the HCC patients before treatment and without remission after treatment and the remission patients after treatment were respectively compared with those of the patients with chronic hepatopathy or hepatocirrhosis by the Mann-Whitney test.The diagnostic efficiency and correlation degree of single and combined detection of five tumor markers in the HCC patients before treatment and without remission after treatment were evaluated by the receiver operating characteristic curve(ROC)and Logistic regression.The positive rates of single and combined detection of five tumor markers and methodology for the diagnosis of HCC were also evaluated.Results There were significant differences in five tumor markers between the HCC patients before treatment and without remission after treatment or with remission after treatment and the patients with chronic hepatopathy and hepatocirrhosis(P<0.05).The areas under the ROC curve(AUCROC),sensitivity,specificity and Youden indexes of five tumor markers for the diagnosis of HCC before treatment and without remission after treatment were 0.800-0.914,69.04%-82.94%,78.34%-98.22%and 0.476-0.812,respectively,and the cut off values of AFP,AFP-L3,AFP-L3%,DCP and GP73 were 7.72 ng/mL,0.60 ng/mL,5.0%,36.79 ng/mL and 78.97 ng/mL,respectively.The AUCROC,sensitivity,specificity and Youden indexes of the combined detection of five tumor markers for the diagnosis of HCC before treatment and without remission after treatment were 0.928-0.996,83.20%-97.67%,94.89%-98.12%and 0.811-0.955,respectively.The positive rates of single detection of five tumor markers were 0.63%(AFP-L3%)-6.37%(AFP)for the patients with chronic hepatopathy and hepatocirrhosis,32.06%(GP73)-79.77%(AFP)for the HCC patients before treatment and without remission after treatment,and 5.77%(AFP-L3%)-17.63%(DCP)for the HCC patients with remission after treatment,respectively.The positive rates of combined detection of five tumor markers were 3.67%(AFP-L3%+GP73)-11.82%(combined detection of five markers)for the patients with chronic hepatopathy and hepatocirrhosis,85.80%(AFP+AFP-L3%)-99.82%(combined detection of five markers)for the HCC patients before treatment and without remission after treatment,and 12.67%(AFP+AFP-L3%)-32.94%(combined detection of five markers)for the HCC patients with remission after treatment,respectively.The sensitivity,specificity,total accuracy,positive predictive values and negative predictive values of combined detection of five tumor markers for the diagnosis of HHC were 22.62%(GP73)-69.77%(combined detection of five markers),88.18%(combined detection of five markers)-99.37%(AFP-L3%),47.44%(GP73)-75.93%(combined detection of five markers),92.16%(combined detection of five markers)-99.33%(AFP-L3%)and 38.59%(GP73)-59.43%(combined detection of five markers),respectively.Conclusion Five serum tumor markers of the patients with chronic hepatopathy,hepatocirrhosis and HCC before and after treatment may change in different degrees,and their combined detection has important clinical application value in the auxiliary diagnosis and evaluation of therapeutic effect of primary HCC.