The up-regulation of Y-box binding proteins (DNA binding protein A and Y-box binding protein-1) as prognostic markers of hepatocellular carcinoma.
OBJECTIVE
The development of hepatocellular carcinoma is associated with the chronic inflammation of the liver caused by various factors such as hepatitis B or C virus infection. Previously, we reported DNA binding protein A (dbpA) as a candidate molecule that can accelerate inflammation-induced hepatocarcinogenesis. DbpA belongs to the Y-box binding protein family, and Y-box binding protein-1 (YB-1), the prototype member of this family, is reported to be a prognostic marker of malignant diseases other than hepatocellular carcinoma. The purpose of this study is to examine the significance of the expression of dbpA or of the T-to-G transversion in the dbpA promoter region, which enhances the promoter activity in vitro, for the progression of hepatocellular carcinoma.


METHODS
We studied the expression of dbpA (as well as of YB-1) in 82 formalin-fixed hepatocellular carcinoma tissues by immunohistochemistry and determined the sequence of the dbpA promoter region in 42 frozen hepatocellular carcinoma tissues. We examined the relationship between these findings and the clinicopathologic factors of hepatocellular carcinoma patients.


RESULTS
DbpA expression was associated with the advanced stages of hepatocellular carcinoma, and the cases with the nuclear dbpA expression had a poor prognosis. DbpA contributed more significantly to this association than YB-1. Furthermore, the T-to-G transversion in the dbpA promoter region was related to the nuclear localization of dbpA.


CONCLUSIONS
DbpA was a more significant prognostic marker of hepatocellular carcinoma than YB-1. The T-to-G transversion in the dbpA promoter region was suggested to be a predisposing factor for the progression of hepatocellular carcinoma.
Yasen
Mahmut
M
Second Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Kajino
Kazunori
K
Kano
Sayaka
S
Tobita
Hiroshi
H
Yamamoto
Junji
J
Uchiumi
Takeshi
T
Kon
Shigeyuki
S
Maeda
Masahiro
M
Obulhasim
Gulanbar
G
Arii
Shigeki
S
Hino
Okio
O
D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017354:Point Mutation; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D016019:Survival Analysis; D015854:Up-Regulation; D051840:Y-Box-Binding Protein 1 / Q000032:analysis* / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051840:Y-Box-Binding Protein 1; D004247:DNA