Ratio disruption of the Δ133p53 and TAp53 isoform equilibrium correlates with poor clinical outcome in intrahepatic cholangiocarcinoma

Abstract

All p53 family members are expressed in several isoforms through alternative promoters and alternative splicing. However, the significance of these isoforms is not yet well understood in cholangiocarcinoma (CCA). In this study, we investigated the expression of p53, p63, p73 and their isoforms at the mRNA and protein levels in CCA. The overexpression of ∆133p53 was observed in the CCA cell lines and clinical specimens. Moreover, the high expression of ∆133p53/TAp53 correlated with short overall survival (p<0.001). Defective p53, including mutant and ∆Np53, was associated with poor prognosis (p<0.024). Multivariate analysis demonstrated that ∆133p53/TAp53 and mutant p53 protein may be used as independent prognostic factors for CCA. To our knowledge, this is the first report of the use of ∆133p53/TAp53 as a potential biomarker in CCA.