Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC...Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.展开更多
Background:Current surveillance strategies for hepatocellular carcinoma(HCC)among patients with non-alcoholic fatty liver disease(NAFLD)are insufficient.This study aimed to investigate the diagnostic perfor-mance of a...Background:Current surveillance strategies for hepatocellular carcinoma(HCC)among patients with non-alcoholic fatty liver disease(NAFLD)are insufficient.This study aimed to investigate the diagnostic perfor-mance of alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ),lens culinaris agglutinin-reactive fraction of AFP(AFP-L3),and their combinations in HCC underlying NAFLD patients.Methods:Serologic AFP,AFP-L3,and PIVKA-Ⅱ levels in NAFLD patients with and without HCC were mea-sured.By receiver operating characteristic(ROC)analyses,the area under the curve(AUC),sensitivity,and specificity were obtained to evaluate the diagnostic accuracy of each biomarker and their combinations.Results:This study was conducted on 139 patients with NAFLD-HCC and 345 NAFLD controls.The eleva-tion of these three biomarkers was observed in patients with NAFLD-HCC compared to those in NAFLD controls(all P<0.001).When they were analyzed individually,PIVKA-Ⅱ showed the best performance in diagnosing any-stage HCC with an AUC of 0.869,followed by AFP(0.763;vs.PIVKA-Ⅱ,P<0.001)and AFP-L3(0.689;vs.PIVKA-II,P<0.001).When they were analyzed in combination,AFP+PIVKA-Ⅱ yielded the highest AUC(0.906),followed by AFP+PIVKA-II+AFP-L3(0.904;vs.AFP+PIVKA-Ⅱ,P=0.086),PIVKA-Ⅱ+AFP-L3(0.881;vs.AFP+PIVKA-II,P<0.001),and AFP+AFP-L3(0.759;vs.AFP+PIVKA-II,P<0.001).Similar findings were obtained in the subgroup with early-stage NAFLD-HCC,as well as the non-cirrhotic subgroup.Conclusions:These data validated the better diagnostic ability of PIVKA-II than AFP or AFP-L3 alone for diagnosing any-stage HCC among patients with NAFLD,and the combination of AFP+PIVKA-II signifi-cantly improved the diagnostic accuracy of NAFLD-HCC.展开更多
目的探究肿瘤标志物甲胎蛋白(alpha fetal protein,AFP)、异常凝血酶原(PIVKA-Ⅱ)和寡糖链组分的相对含量(G-test)分别在原发性肝癌检测中的临床应用价值。方法选取2017年10月至2017年12月首都医科大学附属北京佑安医院临床诊断原发性肝...目的探究肿瘤标志物甲胎蛋白(alpha fetal protein,AFP)、异常凝血酶原(PIVKA-Ⅱ)和寡糖链组分的相对含量(G-test)分别在原发性肝癌检测中的临床应用价值。方法选取2017年10月至2017年12月首都医科大学附属北京佑安医院临床诊断原发性肝癌(hepatoma carcinoma cell,HCC)组共165例,非肝癌组共142例,分别用仪器检测两组患者AFP、PIVKA-Ⅱ及G-test,通过统计学方法来对肿瘤标志物AFP、PIVKA-Ⅱ和G-test诊断的灵敏度、特异性和准确度进行分析。结果在灵敏度上,G-tes的灵敏度最高(83.6%),AFP的灵敏度最低(16.4%),且差异有统计学意义;在特异性上,AFP的特异性最高(97.9%),G-test的特异性最低(73.2%),且差异有统计学意义;在准确度上,G-test的准确度最高(78.8%),AFP的准确度最低(54.1%),且差异有统计学意义。联合检测时G-test+PIVKA-Ⅱ的ROC曲线下面积(area under the curve,AUC)与G-tesT+AFP的AUC一样(86.3%),高于AFP+PIVKA-Ⅱ的AUC(68.3%),G-test+AFP+PIVKA-Ⅱ的AUC为86.4%,灵敏度为93.3%。结论G-test诊断原发性肝癌的价值较AFP、PIVKA-Ⅱ高,AFP诊断灵敏度最高,联合检测时可提高检测率,G-test值较传统的原发性肝癌肿瘤标志物对原发性肝癌的检出率更高,意义更大。展开更多
目的观察肝癌组织中维生素K缺乏或拮抗剂-Ⅱ诱导的蛋白质(protein induced by vitamin K absence or antagonist-Ⅱ,PIVKA-Ⅱ)表达情况及维生素K_2(vitamin K_2,VitK_2)对肝癌细胞中PIVKA-Ⅱ的影响,探讨PIVKA-Ⅱ与肝癌的关系及可能机制...目的观察肝癌组织中维生素K缺乏或拮抗剂-Ⅱ诱导的蛋白质(protein induced by vitamin K absence or antagonist-Ⅱ,PIVKA-Ⅱ)表达情况及维生素K_2(vitamin K_2,VitK_2)对肝癌细胞中PIVKA-Ⅱ的影响,探讨PIVKA-Ⅱ与肝癌的关系及可能机制。方法选择浙江省肿瘤医院、浙江省中山医院2012年1月—2015年12月100对手术切除的原发性肝癌组织及癌旁组织标本,采用ABC免疫组织化学法测定组织中PIVKA-Ⅱ的阳性表达情况,采用化学发光免疫分析法测定标本中PIVKA-Ⅱ水平;将HepG-2细胞和浓度为20μM的VitK_2共同培养,酶联免疫吸附(ELISA)法测定VitK_2对HepG-2肝癌细胞PIVKA-Ⅱ表达的影响,MTT法测定VitK_2对HepG-2肝癌细胞生长的影响,Transwell法测定VitK_2对HepG-2肝癌细胞侵袭能力的影响。结果肝癌组织中PIVKA-Ⅱ阳性率(74.0%)高于癌旁组织中PIVKA-Ⅱ阳性表达率(25.0%,P<0.05);肝癌组织中PIVKA-Ⅱ水平(3 786.23±143.24)m AU/g高于癌旁组织中PIVKA-Ⅱ水平(167.34±21.54)m AU/g,P<0.05。对照组肝癌细胞PIVKA-Ⅱ水平为(3.43±0.04)ng/(ml·10~6细胞),VitK_2组肝癌细胞PIVKA-Ⅱ水平为(2.57±0.02)ng/(ml·10~6细胞),VitK_2组肝癌细胞PIVKA-Ⅱ水平明显低于对照组(P<0.05)。VitK_2与HepG-2肝癌细胞共同培养,第1天、第2天、第3天、第4天、第5天、第6天时VitK_2对HepG-2细胞的抑制率分别为9.2%、16.5%、26.7%、34.8%、41.2%、46.7%。VitK_2与HepG-2肝癌细胞培养24 h后,VitK_2对HepG-2肝癌细胞侵袭的抑制率为37.2%。结论肝癌组织中PIVKA-Ⅱ呈高表达,VitK_2能够降低肝癌细胞中PIVKA-Ⅱ水平、抑制肝癌细胞生长、降低肝癌细胞侵袭能力。展开更多
目的:探讨血清生物标志物甲胎蛋白(AFP)、维生素K缺失或拮抗剂Ⅱ诱导的蛋白质(PIVKA-Ⅱ)和磷脂酰肌醇蛋白聚糖3(GPC-3)单独或联合用于肝细胞癌(以下简称肝癌)诊断的价值。方法:检索PubMed、Web of Science、Embase三个数据库,收集2002...目的:探讨血清生物标志物甲胎蛋白(AFP)、维生素K缺失或拮抗剂Ⅱ诱导的蛋白质(PIVKA-Ⅱ)和磷脂酰肌醇蛋白聚糖3(GPC-3)单独或联合用于肝细胞癌(以下简称肝癌)诊断的价值。方法:检索PubMed、Web of Science、Embase三个数据库,收集2002年以来发表的AFP、PIVKA-Ⅱ和GPC-3单独或联合用于诊断肝癌的文献。根据纳入和排除标准筛选文献并提取相关数据。利用诊断准确性研究的质量评价(QUADAS)检查表对纳入的文献进行质量评价,并采用Meta DiSc软件、Review Manager 5.4软件和Stata 15.1软件对AFP、PIVKA-Ⅱ和GPC-3单用和联合使用诊断肝癌的受试者工作特征曲线下面积(AUC)、敏感度、特异度等指标进行数据分析。结果:共纳入32篇文献。Meta分析结果显示,单个标志物用于诊断肝癌时,PIVKA-Ⅱ的AUC值最高,为0.88(95%CI:0.85~0.91),其次是GPC-3和AFP;多个标志物联合用于诊断肝癌的AUC均高于单个标志物,其中PIVKA-Ⅱ联合GPC-3诊断的AUC值最高,为0.90(95%CI:0.87~0.92)。单个标志物用于诊断肝癌时,PIVKA-Ⅱ和GPC-3的敏感度相对较高(分别为0.75和0.76),但GPC-3的特异度不如PIVKA-Ⅱ和AFP(AFP、PIVKA-Ⅱ和GPC-3分别为0.87、0.88和0.81);多个标志物联合用于诊断肝癌的敏感度较单个标志物诊断时有所提高,但特异度无明显提高。单个标志物用于诊断肝癌时,PIVKA-Ⅱ的诊断比值比(DOR)最高,为22(95%CI:13~36),其次是GPC-3和AFP;两个标志物联合用于诊断肝癌的DOR均高于单个标志物,其中AFP联合GPC-3诊断的DOR最高,为25(95%CI:9~67);三个标志物联合用于诊断肝癌时的DOR明显降低,为10(95%CI:7~45)。结论:单个标志物用于肝癌诊断时,PIVKA-Ⅱ的诊断价值更高。两种标志物联合能显著提高肝癌诊断的敏感度,三种标志物联合未能进一步提高诊断价值。结合临床实际,推荐AFP联合PIVKA-Ⅱ用于肝癌的诊断。展开更多
基金supported in part by the National Natural Sci-ence Foundation of China(81472284 and 81672699)Shanghai Pujiang Program(16PJD004)
文摘Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.
基金the National Natural Science Foundation of China(81972726,81871949 and 82171834)Jiangsu Six Talent Peaks Project(WSN-102).
文摘Background:Current surveillance strategies for hepatocellular carcinoma(HCC)among patients with non-alcoholic fatty liver disease(NAFLD)are insufficient.This study aimed to investigate the diagnostic perfor-mance of alpha-fetoprotein(AFP),protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ),lens culinaris agglutinin-reactive fraction of AFP(AFP-L3),and their combinations in HCC underlying NAFLD patients.Methods:Serologic AFP,AFP-L3,and PIVKA-Ⅱ levels in NAFLD patients with and without HCC were mea-sured.By receiver operating characteristic(ROC)analyses,the area under the curve(AUC),sensitivity,and specificity were obtained to evaluate the diagnostic accuracy of each biomarker and their combinations.Results:This study was conducted on 139 patients with NAFLD-HCC and 345 NAFLD controls.The eleva-tion of these three biomarkers was observed in patients with NAFLD-HCC compared to those in NAFLD controls(all P<0.001).When they were analyzed individually,PIVKA-Ⅱ showed the best performance in diagnosing any-stage HCC with an AUC of 0.869,followed by AFP(0.763;vs.PIVKA-Ⅱ,P<0.001)and AFP-L3(0.689;vs.PIVKA-II,P<0.001).When they were analyzed in combination,AFP+PIVKA-Ⅱ yielded the highest AUC(0.906),followed by AFP+PIVKA-II+AFP-L3(0.904;vs.AFP+PIVKA-Ⅱ,P=0.086),PIVKA-Ⅱ+AFP-L3(0.881;vs.AFP+PIVKA-II,P<0.001),and AFP+AFP-L3(0.759;vs.AFP+PIVKA-II,P<0.001).Similar findings were obtained in the subgroup with early-stage NAFLD-HCC,as well as the non-cirrhotic subgroup.Conclusions:These data validated the better diagnostic ability of PIVKA-II than AFP or AFP-L3 alone for diagnosing any-stage HCC among patients with NAFLD,and the combination of AFP+PIVKA-II signifi-cantly improved the diagnostic accuracy of NAFLD-HCC.
文摘目的探究肿瘤标志物甲胎蛋白(alpha fetal protein,AFP)、异常凝血酶原(PIVKA-Ⅱ)和寡糖链组分的相对含量(G-test)分别在原发性肝癌检测中的临床应用价值。方法选取2017年10月至2017年12月首都医科大学附属北京佑安医院临床诊断原发性肝癌(hepatoma carcinoma cell,HCC)组共165例,非肝癌组共142例,分别用仪器检测两组患者AFP、PIVKA-Ⅱ及G-test,通过统计学方法来对肿瘤标志物AFP、PIVKA-Ⅱ和G-test诊断的灵敏度、特异性和准确度进行分析。结果在灵敏度上,G-tes的灵敏度最高(83.6%),AFP的灵敏度最低(16.4%),且差异有统计学意义;在特异性上,AFP的特异性最高(97.9%),G-test的特异性最低(73.2%),且差异有统计学意义;在准确度上,G-test的准确度最高(78.8%),AFP的准确度最低(54.1%),且差异有统计学意义。联合检测时G-test+PIVKA-Ⅱ的ROC曲线下面积(area under the curve,AUC)与G-tesT+AFP的AUC一样(86.3%),高于AFP+PIVKA-Ⅱ的AUC(68.3%),G-test+AFP+PIVKA-Ⅱ的AUC为86.4%,灵敏度为93.3%。结论G-test诊断原发性肝癌的价值较AFP、PIVKA-Ⅱ高,AFP诊断灵敏度最高,联合检测时可提高检测率,G-test值较传统的原发性肝癌肿瘤标志物对原发性肝癌的检出率更高,意义更大。
文摘目的观察肝癌组织中维生素K缺乏或拮抗剂-Ⅱ诱导的蛋白质(protein induced by vitamin K absence or antagonist-Ⅱ,PIVKA-Ⅱ)表达情况及维生素K_2(vitamin K_2,VitK_2)对肝癌细胞中PIVKA-Ⅱ的影响,探讨PIVKA-Ⅱ与肝癌的关系及可能机制。方法选择浙江省肿瘤医院、浙江省中山医院2012年1月—2015年12月100对手术切除的原发性肝癌组织及癌旁组织标本,采用ABC免疫组织化学法测定组织中PIVKA-Ⅱ的阳性表达情况,采用化学发光免疫分析法测定标本中PIVKA-Ⅱ水平;将HepG-2细胞和浓度为20μM的VitK_2共同培养,酶联免疫吸附(ELISA)法测定VitK_2对HepG-2肝癌细胞PIVKA-Ⅱ表达的影响,MTT法测定VitK_2对HepG-2肝癌细胞生长的影响,Transwell法测定VitK_2对HepG-2肝癌细胞侵袭能力的影响。结果肝癌组织中PIVKA-Ⅱ阳性率(74.0%)高于癌旁组织中PIVKA-Ⅱ阳性表达率(25.0%,P<0.05);肝癌组织中PIVKA-Ⅱ水平(3 786.23±143.24)m AU/g高于癌旁组织中PIVKA-Ⅱ水平(167.34±21.54)m AU/g,P<0.05。对照组肝癌细胞PIVKA-Ⅱ水平为(3.43±0.04)ng/(ml·10~6细胞),VitK_2组肝癌细胞PIVKA-Ⅱ水平为(2.57±0.02)ng/(ml·10~6细胞),VitK_2组肝癌细胞PIVKA-Ⅱ水平明显低于对照组(P<0.05)。VitK_2与HepG-2肝癌细胞共同培养,第1天、第2天、第3天、第4天、第5天、第6天时VitK_2对HepG-2细胞的抑制率分别为9.2%、16.5%、26.7%、34.8%、41.2%、46.7%。VitK_2与HepG-2肝癌细胞培养24 h后,VitK_2对HepG-2肝癌细胞侵袭的抑制率为37.2%。结论肝癌组织中PIVKA-Ⅱ呈高表达,VitK_2能够降低肝癌细胞中PIVKA-Ⅱ水平、抑制肝癌细胞生长、降低肝癌细胞侵袭能力。
