Protein induced by vitamin K absence or antagonist II: Experience to date and future directions

Dong, Libin; Qiu, Xun; Gao, Fengqiang; Wang, Kai; Xu, Xiao

doi:10.1016/j.bbcan.2023.189016

Cited by 8 publications

(1 citation statement)

References 122 publications

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“…作为发生率和病死率均较高的恶性肿瘤［ 42 ］，肝癌的早筛、早诊极为重要。长期以来，血清学标志物AFP因其具有样本易获得、创伤小、可重复等特点已广泛应用于肝癌的筛查和预警［ 43 - 45 ］。1956年，AFP在人胎儿血清中首次发现［ 46 ］。从妊娠第四周开始，由于胎儿肝脏等器官的分泌，AFP水平持续升高［ 47 ］，待胎儿出生后则持续下降并维持在极低水平，但在肝癌发生时其水平又会异常上升。有研究认为，肝癌患者血清AFP水平升高与位于人类4号染色体长臂上的相关基因有关，该基因上的独立增强子抑制的阻断和沉默子的缺失导致启动子的活性恢复，最终使得AFP过表达［ 1 ， 48 ］。也有研究证明，AFP可以通过启动环AMP-蛋白激酶A途径、钙离子内流和caspase-3介导的凋亡信号促进肿瘤增殖［ 49 - 51 ］。但是，临床上有约30%的AFP阴性肝癌患者，且其特异度较低，所以目前AFP用于诊断肝癌饱受争议［ 52 ］。目前研究显示，PIVKA-Ⅱ诊断肝癌的效能高于AFP，有着较高的敏感度和特异度［ 5 ］。PIVKA-Ⅱ可通过增强细胞增殖、肿瘤血管生成等方式促进肿瘤的增殖和转移［ 53 ］。目前，PIVKA-Ⅱ在肝癌中过表达的机制尚无定论，肝癌中PIVKA-Ⅱ过表达可能与缺氧微环境、维生素K代谢受损及凝血酶原前体过表达相关。但是，PIVKA-Ⅱ水平不仅在肝癌患者血清中升高，在维生素K缺乏症及服用维生素K拮抗剂患者的血液中也会异常升高，这也使得PIVKA-Ⅱ在诊断肝癌时存在一定局限［ 54 ］。GPC-3是GPC家族一员，在正常肝脏组织中几乎不表达，但其在肝癌组织中的阳性率高达90%。其通过Wnt/β-catenin信号通路参与肝癌的发生、增殖和转移，是肝癌的重要血清标志物之一［ 55 ］。…”

Section: 讨论unclassified

Combination of serum alpha-fetoprotein, PIVKA-Ⅱ and glypican-3 in diagnosis of hepatocellular carcinoma: a meta-analysis

SONG,

WANG,

ZHANG

et al. 2024

J Zhejiang Univ (Med Sci)

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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。

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Section: 讨论unclassified

Combination of serum alpha-fetoprotein, PIVKA-Ⅱ and glypican-3 in diagnosis of hepatocellular carcinoma: a meta-analysis

SONG,

WANG,

ZHANG

et al. 2024

J Zhejiang Univ (Med Sci)

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Virtual screening and network pharmacology-based synergistic coagulation mechanism identification of multiple components contained in compound Kushen Injection against hepatocellular carcinoma

Zhou,

Xie,

Liu

et al. 2024

Journal of Ayurveda and Integrative Medicine

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Prognostic significance of postoperative serological incomplete conversion of AFP and PIVKA-II after hepatic resection for hepatocellular carcinoma: a multicenter analysis of 1755 patients

Wang,

Qian,

Xiao

et al. 2024

The Oncologist

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Background The value of serum biomarkers, particularly alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), gains increasing attention in prognostic evaluation and recurrence monitoring for patients with hepatocellular carcinoma (HCC). This study investigated the implications of serological incomplete conversion (SIC) of these 2 biomarkers as prognostic indicators for long-term outcomes after HCC resection. Methods A multicenter observational study was conducted on a cohort of HCC patients presenting with AFP (>20 ng/mL) or PIVKA-II (>40 mAU/mL) positivity who underwent curative-intent resection. Based on their postoperative AFP and PIVKA-II levels at first postoperative follow-up (4~8 weeks after surgery), these patients were stratified into the serological incomplete conversion (SIC) and serological complete conversion (SCC) groups. The study endpoints were recurrence and overall survival (OS). Results Among 1755 patients, 379 and 1376 were categorized as having SIC and SCC, respectively. The SIC group exhibited 1- and 5-year OS rates of 67.5% and 26.3%, with the corresponding recurrence rates of 53.2% and 79.0%, respectively; while the SCC group displayed 1- and 5-year OS rates of 95.8% and 62.5%, with the corresponding recurrence rates of 16.8% and 48.8%, respectively (both P < .001). Multivariate Cox regression analysis demonstrated that postoperative SIC was an independent risk factor for both increased recurrence (HR: 2.40, 95% CI, 2.04-2.81, P < .001) and decreased OS (HR: 2.69, 95% CI, 2.24-3.24, P < .001). Conclusion The results emphasize that postoperative incomplete conversion of either AFP or PIVKA-II is a significant prognostic marker, indicating a higher risk for adverse oncologic outcomes following HCC resection. This revelation has crucial implications for refining postoperative adjuvant therapy and surveillance strategies for HCC patients.

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Protein induced by vitamin K absence or antagonist II: Experience to date and future directions

Cited by 8 publications

References 122 publications

Combination of serum alpha-fetoprotein, PIVKA-Ⅱ and glypican-3 in diagnosis of hepatocellular carcinoma: a meta-analysis

Combination of serum alpha-fetoprotein, PIVKA-Ⅱ and glypican-3 in diagnosis of hepatocellular carcinoma: a meta-analysis

Virtual screening and network pharmacology-based synergistic coagulation mechanism identification of multiple components contained in compound Kushen Injection against hepatocellular carcinoma

Prognostic significance of postoperative serological incomplete conversion of AFP and PIVKA-II after hepatic resection for hepatocellular carcinoma: a multicenter analysis of 1755 patients

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