1. JAB1 and phospho-Ser10 p27 expression profile determine human hepatocellular carcinoma prognosis.
- Author
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Wang Y, Yu YN, Song S, Li TJ, Xiang JY, Zhang H, Lu MD, Ji F, and Hu LQ
- Subjects
- Adult, Aged, Blotting, Western, COP9 Signalosome Complex, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular mortality, Case-Control Studies, Cyclin-Dependent Kinase Inhibitor p27 genetics, Female, Follow-Up Studies, Humans, Immunoenzyme Techniques, Immunoprecipitation, Liver Neoplasms diagnosis, Liver Neoplasms mortality, Lymphatic Metastasis, Male, Middle Aged, Mutagenesis, Site-Directed, Mutation genetics, Neoplasm Grading, Neoplasm Invasiveness, Neoplasm Recurrence, Local metabolism, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Phosphorylation, Prognosis, Survival Rate, Tumor Cells, Cultured, alpha-Fetoproteins metabolism, Carcinoma, Hepatocellular metabolism, Cyclin-Dependent Kinase Inhibitor p27 metabolism, Intracellular Signaling Peptides and Proteins metabolism, Liver Neoplasms metabolism, Peptide Hydrolases metabolism
- Abstract
Purpose: 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.
- Published
- 2014
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