title: p27 Is a critical prognostic biomarker in non-alcoholic steatohepatitis-related hepatocellular carcinoma.
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.
authors.affiliation: Department of Medical Technology, Niigata University Graduate School of Health Sciences, 2-746 Asahimachi-dori, Chuo-Ku, Niigata 951-8518, Japan. yasunobu@med.niigata-u.ac.jp.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hirose
authors.forename: Mami
authors.initials: M
authors.lastname: Osawa
authors.forename: Shun
authors.initials: S
authors.lastname: Fujimaki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kubota
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism* / Q000401:mortality; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D018572:Disease-Free Survival; D005235:Fatty Liver, Alcoholic / Q000150:complications / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D050760:Cyclin-Dependent Kinase Inhibitor p27