高尔基蛋白73、甲胎蛋白异质体3、甲胎蛋白和α-L-岩藻糖苷酶在肝脏疾病中的诊断价值

目的比较高尔基蛋白73(GP73)、甲胎蛋白异质体3(AFP-L3)、甲胎蛋白(AFP)和α-L-岩藻糖苷酶(AFU)在不同肝脏疾病患者中的意义及其单项或联合检测诊断肝癌的价值。方法对2013年1-12月收治的272例肝癌患者、203例肝硬化患者、248例慢性肝炎患者及210例健康体检者血清中的GP73、AFP-L3、AFP和AFU水平进行检测。非正态分布的数据多组间比较采用Kruskal-Wallis H检验,组间两两比较采用Mann-Whitney U检验,率的比较用卡方检验。ROC曲线绘制分别以健康人组和非肝癌组(健康体检、慢性肝炎、肝硬化)为对照。联合指标先进行Logistic拟合后再做ROC曲线。结果 GP73水平肝硬化组[177.0(116.0,247.0)ng/ml]较肝癌组[141.0(83.3,218.8)ng/ml])和慢性肝炎组[151.0(83.0,235.3)ng/ml]高(U=22 116.5、21 052.0,P均0.05);AFP-L3和AFP在肝癌组中的水平[11.3(4.3,21.2)%,78.4(7.1,2455.8)ng/ml]明显高于肝硬化组[6.0(4.0,8.0)%,10.0(3.8,49.5)ng/ml]和慢性肝炎组[7.0(5.0,9.0)%,18.8(4.4,79.6)ng/ml](P均0.05)。以健康人血清样本为对照绘制的诊断肝癌的ROC曲线,GP73、AFP-L3、AFP和AFU的ROC曲线下面积(AUC)分别为0.827、0.817、0.901和0.680。由此可知在鉴别健康人和肝癌患者方面,前3者比AFU有较高的准确性。以非肝癌患者血清样本为对照绘制的诊断肝癌的ROC曲线,4个指标对应的AUC分别为0.573、0.734、0.753和0.552,可见AFP-L3和AFP对于诊断肝癌有一定的准确性,其敏感性和特异性达到最大时的cut off值依次为8.55%(56.6%,84.9%),49.88 ng/ml(57.7%,80.9%)。结论 GP73的上升与肝损伤及长期纤维化有关,其在诊断肝脏疾病中有较好的敏感性,AFP-L3和AFP在诊断肝癌方面特异性较好,AFP-L3和AFP两者联合应用可提高肝癌的诊断敏感性至62.1%。

Diagnostic values of GP73,AFP-L3,AFP,and AFU for liver diseases

Objective To compare the levels of Golgi glycoprotein 73 （GP73 ）,alpha-fetoprotein heterogeneity 3 （AFP-L3 ）,alpha-fetoprotein （AFP）,and α-L-fucosidase （AFU）between patients with different liver diseases and the diagnostic value of any or a combi-nation of these makers for liver cancer.Methods The 272 patients with liver cancer,203 patients with liver cirrhosis,and 248 patients with chronic hepatitis admitted to our hospital from January to December,2013,as well as 210 healthy individuals,were included in the study.Serum levels of GP73,AFP-L3,AFP,and AFU were determined.Comparison of non -normally distributed data was made by Kruskal-Wallis H test,and multiple comparisons were made by Mann-Whitney U test.Comparison of rates was made by chi-square test. P〈0.05 was considered significantly different.Receiver operating characteristic （ROC）curves were drawn with healthy individuals and pa-tients with chronic hepatitis or liver cirrhosis as controls,and Logistic fitting and ROC analysis were used to evaluate the diagnostic values of these markers.Results The GP73 level of liver cirrhosis group （177.0 （116.0,247.0）ng/ml）was significantly higher than those of liver cancer group （141.0 （83.3,218.8）ng/ml）and chronic hepatitis group （151.0 （83.0,235.3）ng/ml）（U=22 116.5 and 21 052.0,P〈0.05 for both）.The AFP-L3 and AFP levels of liver cancer group （11.3 （4.3,21.2）%and 78.4 （7.1,2455.8）ng/ml）were significantly higher than those of liver cirrhosis group （6.0 （4.0,8.0）%and 10.0 （3.8,49.5）ng/ml）and chronic hepatitis group （7.0 （5.0,9.0）%and 18.8 （4.4,79.6）ng/ml）（U=16009.0/16083.5 and 22456.5/22346.5,P〈0.05 for all）.According to the ROC curves drawn u-sing healthy individuals as a control,the areas under the ROC curve （AUCs）for GP73,AFP-L3,AFP,and AFU were 0.827,0.817, 0.901,and 0.680,respectively;GP73,AFP-L3,and AFP had a higher diagnostic accuracy for liver cancer than AFU.According to the ROC curves drawn using non-liver cancer p