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BMC Cancer
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Integral analysis of p53 and its value as prognostic factor in sporadic colon cancer

Authors: Arantza Fariña Sarasqueta, Giusi Irma Forte, Wim E Corver, Noel F de Miranda, Dina Ruano, Ronald van Eijk, Jan Oosting, Rob AEM Tollenaar, Tom van Wezel, Hans Morreau

Published in: BMC Cancer | Issue 1/2013

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Abstract

Background

p53 (encoded by TP53) is involved in DNA damage repair, cell cycle regulation, apoptosis, aging and cellular senescence. TP53 is mutated in around 50% of human cancers. Nevertheless, the consequences of p53 inactivation in colon cancer outcome remain unclear. Recently, a new role of p53 together with CSNK1A1 in colon cancer invasiveness has been described in mice.

Methods

By combining data on different levels of p53 inactivation, we aimed to predict p53 functionality and to determine its effects on colon cancer outcome. Moreover, survival effects of CSNK1A1 together with p53 were also studied.
Eighty-three formalin fixed paraffin embedded colon tumors were enriched for tumor cells using flow sorting, the extracted DNA was used in a custom SNP array to determine chr17p13-11 allelic state; p53 immunostaining, TP53 exons 5, 6, 7 and 8 mutations were determined in combination with mRNA expression analysis on frozen tissue.

Results

Patients with a predicted functional p53 had a better prognosis than patients with non functional p53 (Log Rank p=0.009). Expression of CSNK1A1 modified p53 survival effects. Patients with low CSNK1A1 expression and non-functional p53 had a very poor survival both in the univariate (Log Rank p<0.001) and in the multivariate survival analysis (HR=4.74 95% CI 1.45 – 15.3 p=0.009).

Conclusion

The combination of mutational, genomic, protein and downstream transcriptional activity data predicted p53 functionality which is shown to have a prognostic effect on colon cancer patients. This effect was specifically modified by CSKN1A1 expression.
Appendix
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Metadata
Title
Integral analysis of p53 and its value as prognostic factor in sporadic colon cancer
Authors
Arantza Fariña Sarasqueta
Giusi Irma Forte
Wim E Corver
Noel F de Miranda
Dina Ruano
Ronald van Eijk
Jan Oosting
Rob AEM Tollenaar
Tom van Wezel
Hans Morreau
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-277

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