Characteristics of the PIVKA-II found in hepatocellular carcinoma, investigation using monoclonal antibodies MU-3 and 19B7

Sekiya, Chihiro; Kohda, Hironobu; Hasebe, Chitomi; Namiki, Masayoshi; Watanabe, Keisuke; Naraki, Toru

doi:10.1016/0928-4346(94)90063-9

Cited by 4 publications

(7 citation statements)

References 8 publications

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“…The ratio of DCP determined by MU‐3:19B7 (henceforth referred to as the MU‐3:19B7 ratio or the DCP Index) has been measured in patients with liver disease, chronic hepatitis, cirrhosis, and HCC. The ratio was about 1.0–1.5 in patients with chronic hepatitis and cirrhosis and > 2.0 in patients with HCC 12. However, to the best of our knowledge, the relation between this ratio and the prognosis of patients with HCC is not known.…”

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confidence: 83%

The des‐γ‐carboxy prothrombin index is a new prognostic indicator for hepatocellular carcinoma

Nagaoka

Yatsuhashi

Hamada

et al. 2003

Cancer

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BACKGROUND Des‐γ‐carboxy prothrombin (DCP) has been reported to be an important prognostic factor in patients with hepatocellular carcinoma (HCC). Recently, a monoclonal antibody, 19B7, which recognizes the Gla domain of DCP, has been identified. The 19B7 antibody recognizes an epitope different from that recognized by MU‐3, which is another antibody against DCP. In this study, the authors investigated the measurement of DCP using the antibodies MU‐3 and 19B7, respectively, as a prognostic factor for patients with HCC who had solitary, small tumors and or Child Stage A HCC. METHODS One hundred four patients with HCC who had solitary, small tumors or Child Stage A tumors were enrolled in the study between 1991 and 2001. All patients were treated and were followed for a mean of 3.2 years. The authors analyzed the correlation between the DCP Index (DCP measured by MU‐3 and DCP measured by 19B7) and patient prognosis. The patients were classified into 3 groups based on their DCP Index: 1) DCP negative (DCP < 40 milli arbitrary unit (mAU)/mL)); 2) low DCP Index (DCP ≥ 40 mAU/mL; MU‐3:19B7 ratio, < 3.0; and 3) high DCP Index (DCP ≥ 40 mAU/mL; MU‐3:19B7 ratio, ≥ 3.0). RESULTS The survival rate for patients in the high DCP Index group was lower compared with the survival rate for patients in the DCP‐negative group and was significantly lower compared with the survival rate for patients in the low DCP Index group. In a univariate Cox proportional hazards model, the positive factors were high DCP Index and low DCP Index. Among the positive predictive factors that were analyzed using a multivariate Cox proportional hazards model were age (hazard ratio, 3.27; P = 0.006), low DCP Index (hazard ratio, 2.87; P = 0.012), and high DCP Index (hazard ratio, 12.3; P < 0.0001). CONCLUSIONS The prognosis of patients who had a high DCP Index score was poorer compared with patients who had a low DCP Index score and patients who were classified as DCP negative. The authors concluded that the DCP Index is a prognostic indicator for patients with HCC. Cancer 2003;98:2671–7. © 2003 American Cancer Society.

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confidence: 83%

The des‐γ‐carboxy prothrombin index is a new prognostic indicator for hepatocellular carcinoma

Nagaoka

Yatsuhashi

Hamada

et al. 2003

Cancer

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“…Sekiya et al (12) first reported the DCP ratio, which proved useful for the differential diagnosis between DCP produced by a vitamin K deficiency and DCP produced by hepatoma cells. Prothrombin is normally biosynthesized by a conversion of 10 glutamic acid (Glu) residues near the N‐ terminal (Gla domain) of the precursor to gamma‐carboxylation with vitamin K‐dependent gamma‐glutamyl carboxylase (GGC).…”

Section: Methodsmentioning

confidence: 99%

“…The new monoclonal antibody, 19B7, is not only useful for diagnosing hepatocellular carcinoma, but it can also distinguish patients with HCC from those with other pancreatobiliary malignancies when combined with a DCP assay using the conventional monoclonal antibody, MU‐3. Sekiya et al (12) also reported that the DCP ratio defined by DCP measured by MU‐3 antibody/DCP measured by 19B7 antibody demonstrated differences between HCC and benign liver diseases such as chronic hepatitis. Therefore, the DCP ratio may even detect a true DCP produced by hepatoma cells.…”

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confidence: 97%

Des‐gamma‐carboxy prothrombin (DCP) ratio, a novel parameter measured by monoclonal antibodies MU‐3 and 19B7, as a new prognostic indicator for hepatocellular carcinoma

Sugimoto

Takeda

Inoue

et al. 2003

Liver International

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“…Some studies revealed that DCP is not only found in the HCC tissues, but also in the non-cancer tissues surrounding HCC and even in some benign liver diseases, such as acute hepatitis and chronic hepatitis [20,23,24]. These observations imply the complicated causes and mechanisms of DCP production.…”

Section: The Causes and Mechanisms Of Dcp Productionmentioning

confidence: 99%

Des-γ-Carboxy Prothrombin (DCP) as a Potential Autologous Growth Factor for the Development of Hepatocellular Carcinoma

Zhang

Chu

Cui

et al. 2014

Cell Physiol Biochem

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Des-γ-carboxy prothrombin (DCP) is a prothrombin precursor produced in hepatocellular carcinoma (HCC). Because of deficiency of vitamin K or γ-glutamyl carboxylase in HCC cells, the 10 glutamic acid (Glu) residues in prothrombin precursor did not completely carboxylate to γ-carboxylated glutamic acid (Gla) residues, leaving some Glu residues remained in N-terminal domain. These prothrombin precursors with Glu residues are called DCPs. DCP displays insufficient coagulation activity. Since Liebman reported an elevated plasma DCP in patients with HCC, DCP has been used in the diagnosis of HCC. Recently, its biological malignant potential has been specified to describe DCP as an autologous growth factor to stimulate HCC growth and a paracrine factor to integrate HCC with vascular endothelial cells. DCP was found to stimulate HCC growth through activation of the DCP-Met-JAK1-STAT3 signaling pathway. DCP might increase HCC invasion and metastasis through activation of matrix metalloproteinase (MMPs) and the ERK1/2 MAPK signaling pathway. DCP has also been found to play a crucial role in the formation of angiogenesis. DCP could increase the angiogenic factors released from HCC and vascular endothelial cells. These effects of DCP in angiogenesis might be related to activation of the DCP-KDR-PLC-γ-MAPK signaling pathway. In this article, we summarized recent studies on DCP in biological roles related to cancer progression and angiogenesis in HCC.

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Characteristics of the PIVKA-II found in hepatocellular carcinoma, investigation using monoclonal antibodies MU-3 and 19B7

Cited by 4 publications

References 8 publications

The des‐γ‐carboxy prothrombin index is a new prognostic indicator for hepatocellular carcinoma

The des‐γ‐carboxy prothrombin index is a new prognostic indicator for hepatocellular carcinoma

Des‐gamma‐carboxy prothrombin (DCP) ratio, a novel parameter measured by monoclonal antibodies MU‐3 and 19B7, as a new prognostic indicator for hepatocellular carcinoma

Des-γ-Carboxy Prothrombin (DCP) as a Potential Autologous Growth Factor for the Development of Hepatocellular Carcinoma

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Characteristics of the PIVKA-II found in hepatocellular carcinoma, investigation using monoclonal antibodies MU-3 and 19B7

Cited by 4 publications

References 8 publications

The des‐γ‐carboxy prothrombin index is a new prognostic indicator for hepatocellular carcinoma

The des‐γ‐carboxy prothrombin index is a new prognostic indicator for hepatocellular carcinoma

Des‐gamma‐carboxy prothrombin (DCP) ratio, a novel parameter measured by monoclonal antibodies MU‐3 and 19B7, as a new prognostic indicator for hepatocellular carcinoma

Des-&#947;-Carboxy Prothrombin (DCP) as a Potential Autologous Growth Factor for the Development of Hepatocellular Carcinoma

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Des-γ-Carboxy Prothrombin (DCP) as a Potential Autologous Growth Factor for the Development of Hepatocellular Carcinoma