title: Up-regulation of dbpA mRNA in hepatocellular carcinoma associated with metabolic syndrome.
abstract: OBJECTIVE
  Metabolic syndrome (MS) is a group of recognized risk factors for the development of hepatocellular carcinoma (HCC) in patients with chronic liver disease. The aim of this study was to analyze the clinicopathological characteristics of HCC patients with MS and the risk factors for recurrence. Also, the aim was to investigate the cold shock protein: DNA-binding protein A (dbpA) expression in HCC patients with MS.
  
  
  METHODS
  A total of 243 patients who underwent curative resections for HCC were classified into two groups. dbpA expression was investigated in 66 HCC patients with MS and in 30 patients without MS by using real-time RT-PCR. Promoter methylation status was examined by using MS-PCR.
  
  
  RESULTS
  The incidence of metabolic factors affect the HCC significantly higher in non-B non-C patients than in hepatitis B virus (HBV) or hepatitis C virus (HCV) patients (P < 0.001). Univariate analysis of HCC patients with MS recurrence revealed aspartate amino transferase (AST), multiple tumors, liver damage, hepatic vein invasion, advanced cancer stages (P < 0.01), alpha-fetoprotein (AFP) and diabetes mellitus type II (P < 0.05) as risk factors. Multivariate analysis, AST, multiple tumors, and hepatic vein invasion (P < 0.01) were identified as independent factors for the recurrence. dbpA mRNA was higher in patients with MS than in those without MS (P = 0.016), and it was mostly upregulated in non-B non-C HCC patients with MS than in non-B non-C HCC patients without HBV or HCV. Especially, in HCC patients with diabetes mellitus type II, the mRNA and protein levels were highly upregulated. The dbpA expression was regulated by promoter methylation status (P < 0.05).
  
  
  CONCLUSIONS
  This study identifies that dbpA may accelerate the hepatocarcinogenesis in HCC patients with MS via inflammation-induced and oxidative stress pathways. The demethylation-related epigenetic activation may be one of the regulating factors for HCC patients with MS.
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.|Department of Surgery, Xinjiang Uyghur Tumor Hospital of Xinjiang Medical University, 30 Beijing Rood, Urumqi, 830011, Xinjiang, China.
authors.forename: Gulanbar
authors.initials: G
authors.lastname: Obulhasim
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan. mahmut@bioinfo.tmd.ac.jp.|Department of Surgery, Xinjiang Uyghur Tumor Hospital of Xinjiang Medical University, 30 Beijing Rood, Urumqi, 830011, Xinjiang, China. mahmut@bioinfo.tmd.ac.jp.
authors.forename: Mahmut
authors.initials: M
authors.lastname: Yasen
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kajino
authors.affiliation: Department of Computational Biology and Bioinformatics, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Mogushi
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Computational Biology and Bioinformatics, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizushima
authors.affiliation: Department of Computational Biology and Bioinformatics, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Arii
authors.affiliation: Department of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Okio
authors.initials: O
authors.lastname: Hino
keywords: Hepatocellular carcinoma; Metabolic syndrome; Oxidative stress; dbpA expression