血清甲胎蛋白联合维生素K缺乏或拮抗剂Ⅱ诱导蛋白在肝细胞癌病理诊断中的应用价值

Value of serum alpha-fetoprotein and protein induced by vitamin K absence or antagonist-Ⅱ in pathological diagnosis of hepatocellular carcinoma

目的评价血清甲胎蛋白(AFP)及维生素K缺乏或拮抗剂Ⅱ诱导蛋白(PIVKA-Ⅱ)在肝细胞癌(HCC)病理诊断中的价值。方法回顾性研究2016年5月-12月于北京佑安医院肿瘤微创介入中心行超声引导下肝穿刺活组织检查的肝恶性肿瘤患者134例,其中术后病理证实为HCC患者103例,非HCC患者31例,对其血清AFP和PIVKA-Ⅱ的检测结果进行统计分析。2组间比较采用两独立样本秩和检验(Mann Whitney U检验)。采用Spearman秩相关检验分析AFP及PIVKA-Ⅱ的相关性,采用受试者工作特征曲线(ROC曲线)分析AFP及PIVKA-Ⅱ诊断HCC的效能,计算敏感度、特异度及ROC曲线下面积(AUC),AUC比较应用Z检验。结果 HCC组血清AFP和PIVKA-Ⅱ水平均明显高于非HCC组(P值均<0.001);血清AFP诊断HCC的AUC为0.842,PIVKA-Ⅱ诊断HCC的AUC为0.863,二者联合诊断AUC为0.869,三者间差异均有统计学意义(P值均<0.001)。血清AFP单独诊断HCC的敏感度为70.9%,特异度为90.3%;PIVKA-Ⅱ单独诊断HCC的敏感度为72.8%,特异度为77.4%。二者联合检测诊断HCC的敏感度为82.5%,特异度为77.4%。HCC患者血清AFP和PIVKA-Ⅱ表达存在相关性(r=0.207,P<0.05)。结论在肝恶性肿瘤患者中,血清AFP及PIVKA-Ⅱ对HCC的鉴别诊断具有较高的临床价值。PIVKA-Ⅱ单项检测诊断HCC效能优于AFP,二者联合检测诊断HCC效能优于单项检测,血清AFP及PIVKA-Ⅱ检测能够为临床上拒绝行肝穿刺病理检查的肝肿瘤患者病理分型的初步推断提供依据,进而有益于后续规范治疗方案的选择及临床预后的评估。

Objective To investigate the value of serum alpha-fetoprotein（AFP） and protein induced by vitamin K absence or antagonist-II（PIVKA-Ⅱ） in the pathological diagnosis of hepatocellular carcinoma（HCC）.Methods A retrospective analysis was performed for the clinical data of 134 patients with malignant liver tumors who underwent ultrasound-guided liver biopsy in Minimally Invasive Interventional Center of Oncology,Beijing You An Hospital,from May 2016 to December 2016,and among these patients,103 had pathologically confirmed HCC and 31 did not have HCC.A statistical analysis was performed for the measurements of serum AFP and PIVKA-Ⅱ.The Mann Whitney U test was used for comparison between two groups.The Spearman rank correlation analysis was used to analysis the correlation between AFP and PIVKA-Ⅱ.The ROC curve was used to evaluate the efficiency of AFP and PIVKA-Ⅱ in the diagnosis of HCC in patients with malignant liver tumors.Sensitivity and specificity were calculated,and the area under the ROC curve（AUC） was calculated.The Z test was used for the comparison of AUC.Results The HCC group had significantly higher serum levels of AFP and PIVKA-Ⅱ than the non-HCC group（all P〈0.001）.Serum AFP had an AUC of 0.842 in the diagnosis of HCC,PIVKA-Ⅱ had an AUC of 0.863,and combined determination of AFP and PIVKA-Ⅱ had an AUC of 0.869;there was a significant difference in AUC between them（all P〈0.001）.Serum AFP alone had a sensitivity of 70.9% and a specificity of 90.3%,PIVKA-Ⅱ alone had a sensitivity of 72.8% and a specificity of 77.4%,and combined determination of AFP and PIVKA-Ⅱ had a sensitivity of 82.5% and a specificity of 77.4%.In HCC patients,serum AFP was significantly correlated with PIVKA-Ⅱ（r=0.207,P〈0.05）.Conclusion Serum AFP and PIVKA-Ⅱ have a high clinical value in the differential diagnosis of HCC in patients with malignant liver tumors.PIVKA-Ⅱ measured alone has a higher efficiency than AFP,and serum AFP and PIVKA-Ⅱ measured in combination have a higher efficiency than AFP or PIVKA-Ⅱ measured alone.Serum AFP and PIVKA-Ⅱ can provide a basis for preliminary judgment of pathological type in patients who refuse to undergo liver biopsy and help with the selection of standard therapeutic regimens and evaluation of clinical prognosis.