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HCC肿瘤标记物 PIVKA II

维生素K缺乏诱导蛋白(PIVKAII)是一种肿瘤标记物,亦称为des-gamma-carboxy prothrombin(DCP,脱-γ-羧基凝血酶原)。这种蛋白质的表达增加表明发展为肝细胞癌(HCC)的风险较高。将PIVKA II加入到目前对HCC的临床检测中会增加早期检出HCC的几率。

临床意义

研究证实PIVKA II值升高(Cutoff:40mAU/mL)与慢性肝病患者发展为HCC的风险增加有关。PIVKA II是独立于AFP-L3和AFP的用于HCC风险评估的肿瘤标记物。AFP-L3和PIVKA II同时升高指示HCC的进展[1]

据报道,PIVKA II是肝癌发展不同阶段的特异性标记物,其中包括微血管侵犯和门静脉侵袭[2,3]

国际肝病权威组织认为肝硬化患者和慢性乙肝/丙肝患者发展为HCC的风险很高[4-6]。他们建议高危患者参加HCC监测项目,以便及早发现HCC。日本肝病学会建议将超声和肿瘤标记物(包括AFP-L3,AFP和异常凝血酶原(PIVKA II))用于HCC临床监测。对于任何HCC肿瘤标记物升高的患者,应通过加强影像学检查方式进行密切监测[7]

同时检测PIVKA II和AFP-L3具有互补作用,并能有效地及早检出HCC并可对其进行风险评估[1,8,9]

HCC是一种即使在治愈性治疗后也具有较高复发率的癌症。PIVKA II水平较高的患者可能发展为复发性HCC,并且与HCC患者预后不良相关[10]

JSH建议对于治疗后的患者,应结合超声和HCC肿瘤标记物持续对患者进行监测,以便及早发现复发性HCC[6]

如何检测

全自动电泳荧光免疫分析仪µTASWako i30,是用于体外诊断的仪器,能同时测定AFP,AFP-L3和PIVKA II。
请访问"AFP-L3"页面了解更多信息。
PIVKA II和AFP-L3试剂在全球均有销售,在美国和日本已纳入医保。如需了解更多的订购信息,请联系
wako.info02@fujifilm.com

特征

PIVKA II是凝血酶原的一种前体形式。

在正常肝脏中,凝血酶原前体经过转移后羧基化,然后释放到外周血中。羧基化作用将特定的氨基末端谷氨酸残基转化为γ-羧基谷氨酸。

在许多HCC细胞中不存在发生羧基化作用的维生素K依赖性羧化酶,而是分泌一种全部或者部分未转化为谷氨酸的异常凝血酶原。因此,非羧基化形式的凝血酶原(PIVKA II)已被用作HCC的肿瘤标记物[11,12]

PIVKA II亦被成为脱-γ-羧基凝血酶原(des-gamma-carboxy prothrombin, DCP)。

References

  1. Liebman HA, et al. Des-gamma-carboxy (abnormal) prothrombin as a serum marker of primary hepatocellular carcinoma. N. Engl. J. Med. 1984; 310: 1427-31.
  2. Ertle JM, et al. A Combination of a-Fetoprotein and Des-Gamma-Carboxy Prothrombin Is Superior in Detection of Hepatocellular Carcinoma. Digestion. 2013; 87: 121-31.
  3. Choi J, et al. Longitudinal Assessment of Three Serum Biomarkers to Detect Very Early-Stage Hepatocellular Carcinoma. Hepatology. 2018 Aug. 28
  4. Koike Y, et al. Des-gamma-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer 2001 Feb 1; 91(3): 561-9
  5. Yamashita Y, et al. Predictors for microinvasion of small hepatocellular carcinoma ≤ 2 cm. Ann. Surg. Oncol. 2012 Jun; 19(6): 2027-34
  6. Heimbach JK, et al. AASLD Guidelines for the Treatment of Hepatocellular Carcinoma: Hepatology. 2018 Jan; 67 (1): 358-380
  7. EASL Clinical Practice Guideline: Management of hepatocellular carcinoma: J. Hepatol. 69 (2018) 182-236
  8. Kokuno N, et al. Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma: The Japan Society of Hepatology 2013 update (3rd JSH-HCC Guidelines). Hepatol. Res. 2015 Jan 45 (2)
  9. Makuuchi M, et al. Development of evidence-based clinical guidelines for the diagnosis and treatment of hepatocellular carcinoma in Japan. Hepatol. Res. 2008; 38: 37-51.
  10. Shimauchi Y, et al. A simultaneous monitoring of Lens culinaris agglutinin A-reactive alpha-fetoprotein and desgamma-carboxy prothrombin as an early diagnosis of hepatocellular carcinoma in the follow-up of cirrhotic patients. Oncol. Rep. 2000; 7: 249-56.
  11. Hann HW, et al. Usefulness of highly sensitive AFP-L3 and DCP in surveillance for hepatocellular carcinoma in patients with a normal alpha-fetoprotein. J. Med. Microb. Diagn. 2014, 3:1
  12. Koike Y, et al. Des-gamma-carboxy prothrombin as a useful predisposing factor for the development of portal venous invasion in patients with hepatocellular carcinoma: a prospective analysis of 227 patients. Cancer 2001 Feb 1; 91(3): 561-9

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