Ratio disruption of the ∆133p53 and TAp53 isoform equilibrium correlates with poor clinical outcome in intrahepatic cholangiocarcinoma

Nichapavee Nutthasirikul; Temduang Limpaiboon; Chanvit Leelayuwat; Siriporn Patrakitkomjorn; Patcharee Jearanaikoon

doi:10.3892/ijo.2013.1818

Ratio disruption of the ∆133p53 and TAp53 isoform equilibrium correlates with poor clinical outcome in intrahepatic cholangiocarcinoma

Int J Oncol. 2013 Apr;42(4):1181-8. doi: 10.3892/ijo.2013.1818. Epub 2013 Feb 8.

Authors

Nichapavee Nutthasirikul¹, Temduang Limpaiboon, Chanvit Leelayuwat, Siriporn Patrakitkomjorn, Patcharee Jearanaikoon

Affiliation

¹ Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences; Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand.

PMID: 23404110
DOI: 10.3892/ijo.2013.1818

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Bile Duct Neoplasms
Bile Ducts, Intrahepatic
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Cholangiocarcinoma / metabolism*
Cholangiocarcinoma / mortality
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Female
Gene Expression
HeLa Cells
Humans
Kaplan-Meier Estimate
Liver Neoplasms / metabolism*
Liver Neoplasms / mortality
Male
Middle Aged
Molecular Sequence Data
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Prognosis
Protein Isoforms / chemistry
Protein Isoforms / genetics
Protein Isoforms / metabolism
Protein Structure, Tertiary
Transcription Factors / genetics
Transcription Factors / metabolism
Tumor Protein p73
Tumor Suppressor Protein p53 / chemistry
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / metabolism

Substances

Biomarkers, Tumor
DNA-Binding Proteins
Nuclear Proteins
Protein Isoforms
TP53 protein, human
TP63 protein, human
TP73 protein, human
Transcription Factors
Tumor Protein p73
Tumor Suppressor Protein p53
Tumor Suppressor Proteins