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The up-regulation of Y-box binding proteins (DNA binding protein A and Y-box binding protein-1) as prognostic markers of hepatocellular carcinoma.

AbstractPURPOSE:
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.
EXPERIMENTAL DESIGN:
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.
CONCLUSION:
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.
AuthorsMahmut Yasen, Kazunori Kajino, Sayaka Kano, Hiroshi Tobita, Junji Yamamoto, Takeshi Uchiumi, Shigeyuki Kon, Masahiro Maeda, Gulanbar Obulhasim, Shigeki Arii, Okio Hino
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 20 Pg. 7354-61 (Oct 15 2005) ISSN: 1078-0432 [Print] United States
PMID16243807 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Y-Box-Binding Protein 1
  • DNA
Topics
  • Antibodies, Monoclonal (immunology)
  • Antibody Specificity
  • Biomarkers, Tumor (analysis)
  • Carcinoma, Hepatocellular (genetics, metabolism, pathology)
  • Cell Nucleus
  • DNA (chemistry, genetics)
  • DNA Mutational Analysis
  • DNA-Binding Proteins (analysis, genetics, immunology)
  • Immunohistochemistry
  • Liver Neoplasms (genetics, metabolism, pathology)
  • Point Mutation
  • Prognosis
  • Promoter Regions, Genetic (genetics)
  • Survival Analysis
  • Up-Regulation
  • Y-Box-Binding Protein 1 (analysis, genetics, immunology)

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