Novel des-γ-carboxy prothrombin in serum for the diagnosis of hepatocellular carcinoma

Abstract

Background and aim: Serum des-γ-carboxy prothrombin (DCP) levels using a newly developed electrochemiluminescence immunoassay (ECLIA, novel DCP [NX-DCP]) were measured, and the utility of NX-DCP and DCP/NX-DCP ratio for the diagnosis of hepatocellular carcinoma (HCC) was investigated. Antigenic differences in DCP between HCC and non-HCC patients were elucidated.

Methods: The subjects included 170 patients with HCC, 61 with benign liver disease, 12 with obstructive jaundice, and 10 warfarin users. NX-DCP was quantitated by sandwich ECLIA employing novel anti-DCP monoclonal antibodies, P11 and P16. Conventional DCP was quantitated by standard ECLIA. DCP extracted from serum by affinity-chromatography was analyzed by Western blotting.

Results: Conventional serum DCP levels were high in patients with HCC and obstructive jaundice, and in warfarin users, consistent with previous reports. Serum NX-DCP levels were high only in warfarin users and obstructive jaundice patients (vitamin K-deficient patients) but not in HCC patients. The DCP/NX-DCP ratio was significantly higher in the HCC group than in the benign liver disease, obstructive jaundice, and warfarin groups (P < 0.001). Receiver operating characteristic analysis showed significant superiority of the DCP/NX-DCP ratio over conventional DCP as a marker for HCC diagnosis (P < 0.05). Western blot analysis showed that P11 and P16 reacted strongly with DCP from a warfarin user and an obstructive jaundice patient but very faintly with DCP from an HCC patient. Immunohistochemistry on HCC samples and autopsied normal liver tissues from warfarin users showed similar results.

Conclusions: The DCP/NX-DCP ratio is very useful for diagnosing HCC. DCP in HCC patients is distinct from that in vitamin K-deficient patients.

Keywords: des-γ-carboxyl prothrombin; hepatocellular carcinoma; obstructive jaundice; warfarin.