Int. J. Mol. Sci. 2013, 14(12), 23499-23515; doi:10.3390/ijms141223499
Article

p27 Is a Critical Prognostic Biomarker in Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma

1 Department of Medical Technology, Niigata University Graduate School of Health Sciences, 2-746 Asahimachi-dori, Chuo-Ku, Niigata 951-8518, Japan 2 Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-Ku, Niigata 951-8510, Japan 3 Department of Pediatric Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-Ku, Niigata 951-8510, Japan These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 4 September 2013; in revised form: 24 October 2013 / Accepted: 12 November 2013 / Published: 29 November 2013
(This article belongs to the Special Issue Non-Alcoholic Fatty Liver Disease Research)
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Abstract: Non-alcoholic steatohepatitis (NASH) is a recently identified chronic liver disease, which progresses to liver cirrhosis and hepatocellular carcinoma (HCC). As the number of patients studied to date has been limited, clinically useful prognostic biomarkers of NASH-related HCC have not been available. In this study, we investigated the status of a cell-cycle regulator, p27, in NASH-related HCC. p27 has been regarded as a prognostic factor in various types of cancer patients. A total of 22 cases with NASH-related HCC were analyzed for p27 protein expression, and phosphorylation at threonine 157 (T157) and serine 10 (S10) by immunohistochemical analysis. The correlation of p27 with tumor characteristics, disease-free survival (DFS), and overall survival was analyzed. p27 expression was decreased in 13 HCCs (59%), and was significantly correlated with enlarged tumor size (p = 0.01) and increased cell proliferation (p < 0.01). Phospho-p27 at T157 and S10 was detected in four (18%) and seven (32%) cases, respectively, and patients positive for phospho-p27 (S10) showed reduced DFS (hazard ratio 7.623, p = 0.016) by univariate analysis. Further studies with more patients are required to verify the usefulness of p27 as a biomarker for predicting tumor recurrence in NASH patients.
Keywords: p27; nonalcoholic steatohepatitis; hepatocellular carcinoma; prognosis

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MDPI and ACS Style

Matsuda, Y.; Wakai, T.; Hirose, Y.; Osawa, M.; Fujimaki, S.; Kubota, M. p27 Is a Critical Prognostic Biomarker in Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma. Int. J. Mol. Sci. 2013, 14, 23499-23515.

AMA Style

Matsuda Y, Wakai T, Hirose Y, Osawa M, Fujimaki S, Kubota M. p27 Is a Critical Prognostic Biomarker in Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2013; 14(12):23499-23515.

Chicago/Turabian Style

Matsuda, Yasunobu; Wakai, Toshifumi; Hirose, Yuki; Osawa, Mami; Fujimaki, Shun; Kubota, Masayuki. 2013. "p27 Is a Critical Prognostic Biomarker in Non-Alcoholic Steatohepatitis-Related Hepatocellular Carcinoma." Int. J. Mol. Sci. 14, no. 12: 23499-23515.

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