title: JAB1 and phospho-Ser10 p27 expression profile determine human hepatocellular carcinoma prognosis.
abstract: OBJECTIVE
  To elucidate the clinicopathological significance and the role of Jun Activation Domain-Binding Protein 1 (JAB1), Ser10-phosphorylated p27 (p27S10), and total p27 in human hepatocellular carcinoma (HCC) prognosis.
  
  
  METHODS
  We evaluated the expression of JAB1 and p27S10 in tissues by immunohistochemical and immunoblot analyses. p27 Ser10 phosphorylation and Ser10 phosphorylation-dependent p27-JAB1 interaction were demonstrated in proliferating Huh7 cells following transfection of pEGFP-p27WT/p27S10A/p27S10D plasmids and pcDNA3.1-p27WT/p27S10A/p27S10D-Myc plasmids. Univariate and multivariate analysis were used to determine their role in HCC prognosis.
  
  
  RESULTS
  JAB1 and p27S10 are overexpressed in HCC samples compared with paired normal tissues. There was a strong correlation between JAB1 and p27S10 expression (P < 0.001), and expression of both inversely correlated with total p27 levels (P < 0.001). High JAB1 and p27S10 expression correlated with histological grade, vascular invasion, and serum α-fetoprotein (AFP) level (all P < 0.01). Total p27 expression also correlated with histological tumor grade (P = 0.048) and AFP level (P = 0.015). The p27S10(high)/JAB1(high)/p27(1ow) profile was the most reliable indication of poor prognostic. Ser10 phosphorylation increased and total p27 levels decreased in a time-dependent manner in serum-starved Huh7 cells following addition of serum. Immunoprecipitation analysis revealed that p27 Ser-to-Asp substitution at position 10 (S10D) markedly enhanced the interaction between JAB1 and p27, but replacement of S10A reduced binding.
  
  
  CONCLUSIONS
  This study revealed that combined JAB1, p27S10, and total p27 expression may serve as a prognostic marker for HCC.
authors.affiliation: Shanghai Key Laboratory of Gynecologic Oncology, Focus Construction Subject of Shanghai Education Department, Shanghai, 200127, China.
authors.forename: You
authors.initials: Y
authors.lastname: Wang
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Yu
authors.forename: Shu
authors.initials: S
authors.lastname: Song
authors.forename: Tie-Jun
authors.initials: TJ
authors.lastname: Li
authors.forename: Jing-Ying
authors.initials: JY
authors.lastname: Xiang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Mu-Dan
authors.initials: MD
authors.lastname: Lu
authors.forename: Fang
authors.initials: F
authors.lastname: Ji
authors.forename: Ling-Qing
authors.initials: LQ
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D000075686:COP9 Signalosome Complex; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D016022:Case-Control Studies; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008113:Liver Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D010447:Peptide Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; D000509:alpha-Fetoproteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex