Distribution of the heterogeneity of des-gamma-carboxyprothrombin in patients with hepatocellular carcinoma.
OBJECTIVE
Our aim was to evaluate the heterogeneity of des-gamma-carboxyprothrombin (DCP) in the plasma of patients with hepatocellular carcinoma (HCC), benign liver diseases, and normal controls and compare the DCP values by enzyme-linked immunosorbent assay (ELISA) for two types monoclonal antibodies (MU-3 and 19B7).


METHODS
We purified DCP from the plasma of 17 patients with HCC, three patients with metastatic liver tumors (MTLT), 12 with acute hepatitis (AH), five with chronic hepatitis (CH), nine with liver cirrhosis (LC), and 10 normal controls (NC). The DCP was analyzed by using immunoaffinity chromatography, reversed-phase high-performance liquid chromatography and measured by using an ELISA.


RESULTS
In HCC, the synthesis of the 1-, 3-, and 4-Gla (gamma-carboxyglutamic acid) DCP variants markedly increased, and those levels accounted for more than 50% of the DCP. The synthesis of the 3-, and 4-Gla DCP gradually increased in order of AH, CH, and LC patients. The MU-3 antibody reacted with the 1-, 3- and 4-Gla DCP variants, whereas the 19B7 antibody reacted with the 6-, 7- and 8-Gla variants. The DCP was measured by ELISA, markedly increased in order of NC, AH, CH, LC, and HCC cases. The correlation of the ratios (1 + 3 + 4)-Gla/(6 + 7 + 8)-Gla DCP and MU-3/19B7 was positive and statistically significant (r = 0.786, n = 56).


CONCLUSIONS
According to the severity of liver damages, the synthesis of the 1-, 3- and 4-Gla DCP variants that lost the Ca binding from the outside of the Gla-domain of the prothrombin molecule increases and the MU-3/19B7 ratio is believed to reflect this.
Uehara
Soichiro
S
Department of Internal Medicine and Gastroenterology, Ohtakionsen Hospital, Hokkaido, Japan. Ootaki_ph@jyoujinkai.or.jp
Gotoh
Katsuhiro
K
Handa
Hiroshi
H
Tomita
Hiroshi
H
Senshuu
Mitiko
M
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D015415:Biomarkers / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood*; D016022:Case-Control Studies; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D014644:Genetic Variation; D006505:Hepatitis / Q000097:blood; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood; D008113:Liver Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D011516:Prothrombin / Q000235:genetics* / Q000276:immunology
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D011498:Protein Precursors; C008208:acarboxyprothrombin; D011516:Prothrombin