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BMC Cancer

, 13:277

Translational oncology

Abstract

Backgroundp53 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.

MethodsBy 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.

ResultsPatients 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.

ConclusionThe 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.

KeywordsColon cancer p53 Prognosis Survival CSKN1A1 Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-13-277 contains supplementary material, which is available to authorized users.

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Autor: Arantza Fariña Sarasqueta - Giusi Irma Forte - Wim E Corver - Noel F de Miranda - Dina Ruano - Ronald van Eijk - Jan Oo

Fuente: https://link.springer.com/







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