Tumor Biology

, Volume 37, Issue 12, pp 15447–15456 | Cite as

Clinical application of protein induced by vitamin K antagonist-II as a biomarker in hepatocellular carcinoma

  • Hao Xing
  • Cunling Yan
  • Liming Cheng
  • Nianyue Wang
  • Shuyang Dai
  • Jianyong Yuan
  • Wenfeng Lu
  • Zhouchong Wang
  • Jun Han
  • Yijie Zheng
  • Tian Yang


Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Early diagnosis improves the prognosis. Protein induced by vitamin K antagonist-II (PIVKA-II) is an effective serum biomarker for HCC diagnosis and prognosis. Combined with another serum biomarker α-fetoprotein (AFP), the sensitivity and specificity of HCC diagnosis can be improved to a maximum of 94 and 98.5 %, respectively. PIVKA-II alone or in combination with AFP and/or AFP-L3 was effective in predicting the treatment response and clinical outcome of curative hepatic resection, chemotherapy, targeted therapy, radiotherapy, and liver transplantation. Japanese clinical guidelines recommend the combined use of PIVKA-II and AFP for the diagnosis of HCC, management of high-risk population, and prognosis of anticancer treatment. Further, PIVKA-II as a functional target promoted HCC cell proliferation, invasion, and metastasis by activating c-Met and other signal transduction pathways. Inhibition of PIVKA-II may provide a selective and effective therapy for HCC.


Protein induced by vitamin K antagonist-II Biomarker Hepatocellular carcinoma Diagnosis Treatment outcome 



This study was supported by the National Natural Science Foundation of China (Nos. 81472284, 81172020, and 81372262), Program for Excellent Young Scholars of SMMU, and Charitable Project on Scientific Research of Shanghai.

Compliance with ethical standards

Conflicts of interest

Yijie Zheng is an employee of Abbott Diagnostics. There are no other conflicts of interest.


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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Hao Xing
    • 1
  • Cunling Yan
    • 2
  • Liming Cheng
    • 3
  • Nianyue Wang
    • 4
  • Shuyang Dai
    • 1
  • Jianyong Yuan
    • 1
  • Wenfeng Lu
    • 1
  • Zhouchong Wang
    • 1
  • Jun Han
    • 1
  • Yijie Zheng
    • 5
  • Tian Yang
    • 1
  1. 1.Department of Hepatic Surgery, Eastern Hepatobiliary Surgery HospitalSecond Military Medical UniversityShanghaiChina
  2. 2.Department of Clinical LaboratoryPeking University First HospitalBeijingChina
  3. 3.Department of Clinical Laboratory, Tongji HospitalHuazhong University of Science and TechnologyWuhanChina
  4. 4.The Second Hospital of NanjingAffiliated to Medical School of Southeast UniversityNanjingChina
  5. 5.Medical Scientific AffairsAbbott DiagnosticsShanghaiChina

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