联合CA19-9、CA125和CEA检测在AFP阴性的ICC鉴别诊断中的应用价值

目的探讨血清癌抗原19-9（CA19-9）、癌抗原125（CA125）和癌胚抗原（CEA）联合检测在甲胎蛋白（AFP）阴性的肝内胆管细胞癌（ICC）患者诊断中的价值。方法2014年6月~2016年6月我院收治的ICC患者60例,根据AFP检测结果,将其分为AFP阴性组和AFP阳性组,每组分别为30例。采用微阵列酶联免疫分析法（Array-ELISA）检测血清CA19-9、CA125和CEA,采用受试者工作特征曲线（ROC）下面积（AUC）分别对各标记物及联合检测诊断的灵敏度、特异度和正确率进行评估。结果30例AFP阴性组血清CA19-9、CA125和CEA水平分别为138.8（85.7~185.1）U/ml、109.6（48.4~201.8）U/ml、11.2（17.5~21.9）ng/ml,均显著高于AFP阳性组的【（38.0（16.9~75.5）U/ml、18.1（9.3~48.1）U/ml、5.5（3.1~8.5）ng/ml）,P<0.01】;两组血清肿瘤标志物诊断ICC的ROC曲线下面积均呈现出CA19-9>CA125>CEA的趋势,在AFP阴性组,各单项诊断的ROC曲线下面积分别为0.85、0.83和0.81,显著高于AFP阳性组的【（0.55、0.45和0.42）,P<0.05】;在单项诊断ICC时,血清CA19-9、CA125和CEA的最佳临床诊断截断点分别为124.89 U/ml、96.04 U/ml和11.97 ng/ml;血清CA19-9、CA125和CEA诊断ICC的灵敏度、特异度和正确率分别为（73.33%、76.67%和71.67%）、（66.67%、70.00%和68.33%）和（60.00%、70.00%和65.00%）,以CA19-9检测诊断的效能最高;两组联合检测诊断的ROC曲线下面积均高于单项指标检测的ROC曲线下面积,且都表现为（CA19-9/CA125/CEA）>（CA19-9/CA125）>（CA19-9/CEA）>（CA125/CEA）,在AFP阴性组,各联合检测诊断的ROC曲线下面积分别为0.94、0.88、0.86和0.85 ,显著高于在AFP阳性组的【（0.74、0.62、0.58和0.52）,P<0.05】;（CA19-9/CA125/CEA）、（CA19-9/CA125）、（CA19-9/CEA）和（CA125/CEA）四种联合检测诊断的灵敏度、特异度和正确率均提高,分别为（90.00%、90.00%和90.00%）、（83.33%、83.33%和81.67%）、（76.67%、83.33%和80.00%）和（70.00%、76.67%和73.33%）,以CA19-9/CA125/CEA联合检测诊断效能最高。结论我们认为,血清CA19-9、CA125和CEA联合检测可提高对AFP阴性ICC患者诊断的正确率,需要临床扩大验证。

Application of serum CA19-9, CA125 and CEA in diagnosis of serum AFP negative patients with intrahepatic cholangiocarcinoma

Objective To explore the application of serum cancer antigen19-9（CA19-9）,CA125 and carcinoembryonic antige （CEA） in the diagnosis of serum alpha-fetoprotein （AFP） negative patients with intrahepatic cholangiocarcinoma （ICC）. Methods 60 patients with ICC were recruited in our hospital between June 2014 and June 2016,and they were divided into two groups,e.g. AFP-negative group and AFP-positive group with 30 in each group according to the results of serum AFP detection. Serum CA19-9,CA125 and CEA levels were detected by array-ELISA. Receiver operating characteristic（ROC） curves were used to evaluate the diagnostic efficacy of each and joint detection of CA19-9,CA125 and CEA for diagnosis of ICC. Results Serum levels of CA19-9,CA125 and CEA in AFP negative group were 138.8（85.7~185.1）U/ml,109.6（48.4~201.8）U/ml, 11.2（17.5~21.9） ng/ml,much higher than 【（38.0（16.9~75.5）U/ml,18.1（9.3~48.1）U/ml,5.5（3.1~8.5）ng/ml）,P<0.01】 in AFP-positive group;The ROC curve area of serum CA19-9,CA125 and CEA in AFP negative group were 0.85,0.83 and 0.81,respectively,significantly higher than[（0.55,0.45 and 0.42）,P<0.05] in AFP positive group; the cut-off-value of serum CA19-9,CA125 and CEA in diagnosis of ICC were 124.89 U/ml,96.04 U/ml and 11.97 ng/ml respectively;The sensitivity,specificity and accuracy rates of CA19-9,CA125 and CEA were （73.33%,76.67% and 71.67%）,（66.67%,70.00% and 68.33%） and（60.00,70.00% and 65.00）,respectively;ROC curve area under joint detection showed that （CA19-9/CA125/CEA）>（CA19-9/CA125）>（CA19-9/CEA）> （CA125/CEA）,the ROC curve area of joint diagnosis in the AFP negative group were 0.94,0.88,0.86 and 0.85,respectively,significantly higher than those in the AFP positive group [（0.74,0.62,0.58 and 0.52）,P<0.05];the sensitivity,specificity and accuracy of joint detection[（CA19-9/CA125/CEA）,（CA19-9/CA125）,（CA19-9/CEA） and 9CA125/CEA）] increased,and they were（90%,90% and 90%）,（83.33%,83.33% and 81.67%）,（76.67%,83.33% and 80%） and（70%,76.67% and 73.33%）,respectively,with the efficacy of （CA19-9/CA125/CEA） was the best. Conclusion We believe that the combination of serum CA19-9,CA125 and CEA detection can improve the correct diagnosis of serum AFP negative patients with ICC,which needs further clinical investigation.