The Up-Regulation of Y-Box Binding Proteins (DNA Binding Protein A and Y-Box Binding Protein-1) as Prognostic Markers of Hepatocellular Carcinoma

• Published in: Clinical cancer research 2005-10, Vol.11 (20), p.7354-7361
• Main Authors: YASEN, Mahmut, KAJINO, Kazunori, HINO, Okio, KANO, Sayaka, TOBITA, Hiroshi, YAMAMOTO, Junji, UCHIUMI, Takeshi, KON, Shigeyuki, MAEDA, Masahiro, OBULHASIM, Gulanbar, ARII, Shigeki
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - immunology; Antibody Specificity; Biological and medical sciences; Biomarkers, Tumor - analysis; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell Nucleus; DNA - chemistry; DNA - genetics; DNA Mutational Analysis; DNA-Binding Proteins - analysis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - immunology; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal cancers: liver; Immunohistochemistry; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Point Mutation; Prognosis; Promoter Regions, Genetic - genetics; Promoter/enhancer analysis; Survival Analysis; Tumor markers and detection of metastasis; Tumor promotion and progression; Tumors; Up-Regulation; Y-Box-Binding Protein 1 - analysis; Y-Box-Binding Protein 1 - genetics; Y-Box-Binding Protein 1 - immunology
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-1027

Purpose: 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.