Patterns of p73 N-terminal isoform expression and p53 status have prognostic value in gynecological cancers

  • Authors:
    • Kerstin Becker
    • Petr Pancoska
    • Nicole Concin
    • Kelly Vanden Heuvel
    • Neda Slade
    • Margaret Fischer
    • Eva Chalas
    • Ute M. Moll
  • View Affiliations

  • Published online on: October 1, 2006     https://doi.org/10.3892/ijo.29.4.889
  • Pages: 889-902
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Abstract

The goal of this study was to determine whether patterns of expression profiles of p73 isoforms and of p53 mutational status are useful combinatorial biomarkers for predicting outcome in a gynecological cancer cohort. This is the first such study using matched tumor/normal tissue pairs from each patient. The median follow-up was over two years. The expression of all 5 N-terminal isoforms (TAp73, ΔNp73, ΔN'p73, Ex2p73 and Ex2/3p73) was measured by real-time RT-PCR and p53 status was analyzed by immunohistochemistry. TAp73, ΔNp73 and ΔN'p73 were significantly upregulated in tumors. Surprisingly, their range of overexpression was age-dependent, with the highest differences δ (tumor-normal) in the youngest age group. Correction of this age effect was important in further survival correlations. We used all 6 variables (five p73 isoform levels plus p53 status) as input into a principal component analysis with Varimax rotation (VrPCA) to filter out noise from non-disease related individual variability of p73 levels. Rationally selected and individually weighted principal components from each patient were then used to train a support vector machine (SVM) algorithm to predict clinical outcome. This SVM algorithm was able to predict correct outcome in 30 of the 35 patients. We use here a mathematical tool for pattern recognition that has been commonly used in e.g. microarray data mining and apply it for the first time in a prognostic model. We find that PCA/SVM is able to test a clinical hypothesis with robust statistics and show that p73 expression profiles and p53 status are useful prognostic biomarkers that differentiate patients with good vs. poor prognosis with gynecological cancers.

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October 2006
Volume 29 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Becker, K., Pancoska, P., Concin, N., Vanden Heuvel, K., Slade, N., Fischer, M. ... Moll, U.M. (2006). Patterns of p73 N-terminal isoform expression and p53 status have prognostic value in gynecological cancers. International Journal of Oncology, 29, 889-902. https://doi.org/10.3892/ijo.29.4.889
MLA
Becker, K., Pancoska, P., Concin, N., Vanden Heuvel, K., Slade, N., Fischer, M., Chalas, E., Moll, U. M."Patterns of p73 N-terminal isoform expression and p53 status have prognostic value in gynecological cancers". International Journal of Oncology 29.4 (2006): 889-902.
Chicago
Becker, K., Pancoska, P., Concin, N., Vanden Heuvel, K., Slade, N., Fischer, M., Chalas, E., Moll, U. M."Patterns of p73 N-terminal isoform expression and p53 status have prognostic value in gynecological cancers". International Journal of Oncology 29, no. 4 (2006): 889-902. https://doi.org/10.3892/ijo.29.4.889