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Up-regulation of dbpA mRNA in hepatocellular carcinoma associated with metabolic syndrome

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Abstract

Purpose

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.

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Acknowledgements

This work was supported by Special Coordination Funds for Promoting Science and Technology (Japan Science and Technology Agency), and a Grant-in-Aid from Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Pathology and Oncology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Gulanbar Obulhasim, Kazunori Kajino & Okio Hino

  2. Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

    Mahmut Yasen, Shinji Tanaka & Shigeki Arii

  3. Department of Computational Biology and Bioinformatics, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan

    Kaoru Mogushi, Hiroshi Mizushima & Hiroshi Tanaka

  4. Department of Surgery, Xinjiang Uyghur Tumor Hospital of Xinjiang Medical University, 30 Beijing Rood, Urumqi, 830011, Xinjiang, China

    Gulanbar Obulhasim & Mahmut Yasen

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  1. Gulanbar Obulhasim
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  2. Mahmut Yasen
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  3. Kazunori Kajino
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  4. Kaoru Mogushi
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  6. Hiroshi Mizushima
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  7. Hiroshi Tanaka
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  8. Shigeki Arii
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  9. Okio Hino
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Correspondence to Mahmut Yasen.

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Obulhasim, G., Yasen, M., Kajino, K. et al. Up-regulation of dbpA mRNA in hepatocellular carcinoma associated with metabolic syndrome. Hepatol Int 7, 215–225 (2013). https://doi.org/10.1007/s12072-012-9357-4

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  • DOI: https://doi.org/10.1007/s12072-012-9357-4

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