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

Abstract

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.

Diagnostic Accuracy of PIVKA-II, Alpha-Fetoprotein and a Combination of both in Diagnosis of Hepatocellular Carcinoma in Patients Affected by Chronic HCV Infection

“…In our study, we showed that higher serum concentrations of both PIVKA-II and AFP, were significantly-related to diagnosis of HCC. This is in accordance with other authors, who showed the production of PIVKA-II by HCC and its role as an autologous growth, invasive and pro-angiogenetic factor (11-13) as well as its absence in non-neoplastic hepatic diseases (10).…”

“…PIVKA II is not elevated in benign hepatic diseases (e.g. cirrhosis, necrosis) (10,18), while it is elevated in HCC at early stage as well as in HCC nodules of all sizes (8,18,19).…”

“…It is synthesized in the presence of acquired defects of precursor carboxylation found in patients with HCC (5,10). PIVKA-II may have a role in HCC progression by acting as an autologous growth factor (11)(12)(13).…”

HULC and Linc00152 Act as Novel Biomarkers in Predicting Diagnosis of Hepatocellular Carcinoma

“…The half of new cases of death occurs in China every year [1][2][3]. The prognosis of patients with HCC is poor and once HCC invades other organs and tissues or spreads distantly, the clinical outcome may be even worse [4][5]. Therefore, early detection of HCC is of great importance.…”

Des-Gamma-Carboxy Prothrombin (DCP) Antagonizes the Effects of Gefitinib on Human Hepatocellular Carcinoma Cells

“…Thus, DCP continues to be used as a diagnostic marker, and DCP is also a promising target for development of HCC chemotherapy. Development of DCP inhibitors and their use might improve the efficacy of gefitinib and many other tyrosine kinase inhibitors for the treatment of HCC [20,41]. …”