VKORC1 haplotypes influence the performance characteristics of PIVKAII for screening of hepatocellular carcinoma.
BACKGROUND
PIVKAII (protein induced by vitamin K absence), used for screening for hepatocellular carcinoma (HCC), is influenced by vitamin K epoxide reductase complex subunit 1 (VKORC1). VKORC1 haplotype frequency is significantly different in ethnic groups. We evaluated whether VKORC1 haplotypes could influence the performance characteristics of PIVKAII in screening for HCC.


METHODS
A total 228 HCC patients and 258 patients with hepatitis B were recruited. Tumor size was measured in 76 patients with HCC. Serum PIVKAII concentrations and VKORC1 haplotype were determined in the cohort. Youden's index and ROC curves were used to compare the performance characteristics of PIVKAII in screening for HCC.


RESULTS
In the HCC group and in patients with hepatitis B, serum PIVKAII concentrations were higher in VKORC1 rs2395612 TT carriers than in CC/CT carriers (50.34±72.18 vs. 11.98±27.45, p<0.05 in HCC group and 1.92±0.52 vs. 1.48±0.36, p<0.01). The estimated optimal cut-off value of PIVKAII for screening HCC was 2.0 and 3.0 ng/mL in CC/CT carriers and TT carriers, respectively. Furthermore, VKORC1 haplotypes also influenced the association of serum PIVKAII concentrations with HCC tumor size in patients with HCC.


CONCLUSIONS
VKORC1 haplotypes influence the performance characteristics of PIVKAII for screening of HCC. Thus, measurement could be complementary for PIVKAII in HCC screening.
Wang
Yibo
Y
Sino-German Laboratory for Molecular Medicine, FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China. yibowang@hotmail.com
Luo
Fang
F
Zheng
Yi
Y
Fan
Xiaohan
X
Chen
Jinxing
J
Zhang
Yu
Y
Hui
Rutai
R
D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D006239:Haplotypes; D006509:Hepatitis B / Q000097:blood; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011498:Protein Precursors / Q000097:blood / Q000235:genetics*; D011516:Prothrombin / Q000235:genetics*; D064417:Vitamin K Epoxide Reductases
D015415:Biomarkers; D011498:Protein Precursors; C008208:acarboxyprothrombin; D011516:Prothrombin; D004247:DNA; D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases