Vitamin K Contents in Liver Tissue of Hepatocellular Carcinoma Patients

Abstract

Serum protein induced in vitamin K absence-II (PIVKA-II) is used as a tumor marker because it increases at a notably higher rate in patients with hepatocellular carcinoma. To clarify the mechanism causing the elevation of serum PIVKA-II, we measured the contents of vitamins K 1 (phylloquinone, PK) and K 2 (menaquinone, MK) (MK-4, MK-5, MK-6, MK-7, MK-8, MK-9, MK-10) in liver tissue resected from 21 hepatic cancer patients (12 patients with hepatocellular carcinoma and 9 patients with metastatic hepatic cancer), using HPLC combined with coulometric reduction and fluorometric detection. In the cancerous tissue of hepatocellular carcinoma patients, PK, MK-7, MK-8, and MK-10 were significantly lower than that found in the noncancerous tissue. Furthermore, MK-6, MK-7, MK-8, and MK-10 in the cancerous tissue of hepatocellular carcinoma patients were significantly lower than that in the cancerous tissue of metastatic hepatic cancer patients. These data suggested that one of the mechanisms of the elevation of serum PIVKA-II levels in hepatocellular carcinoma patients is a vitamin K deficiency in the local cancerous tissue.

Des‐gamma‐carboxyprothrombin in patients with hepatocellular carcinoma and liver cirrhosis

“…The pathophysiology of hepatocarcinogenesis is closely linked to the evolution of cirrhosis. Although the exact mechanism of DCP production in HCC tissues is yet to be clearly understood, DCP is reportedly produced by malignant hepatocytes that result from an acquired post‐translational defect in the vitamin K‐dependent carboxylase system 23–26 . The absence of vitamin K or the presence of its antagonist inhibiting vitamin K‐dependent carboxylase activity results in the secretion of immature prothrombin lacking gamma‐carboxy‐glutamic acid residues (that is DCP) into the blood.…”

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

“…Vitamin K 2 inhibits the growth of various neoplastic cells, including hepatoma cells, by causing cell-cycle arrest and apoptosis through different proposed mechanisms [116][117][118][119][120][121][122].…”

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

“…During the γ-carboxylation of Glu residues in lumen of endoplasmic reticulum, vitamin K is converted from active form to vitamin K 2,3-epoxide, which must be recycled to the active form by vitamin K epoxide reductase (VKOR) to maintain coagulation cycle [38]. However, vitamin K was found at a lower level in HCC tissues as compared with normal liver tissues [39]. A clear correlation between vitamin K deficiency and DCP production existed in the HCC tissues [40,41].…”