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izvor podataka: crosbi

Patterns of p73 N-terminal isoform expression and p53 status have prognostic value in gynecological cancer (CROSBI ID 125238)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Becker, Kerstin ; Pancoska, Petr ; Concin, Nicole ; Vanden Heuvel, Kelly ; Slade, Neda ; Fischer, Margaret ; Chalas, Eva ; Moll, Ute, M. Patterns of p73 N-terminal isoform expression and p53 status have prognostic value in gynecological cancer // International journal of oncology, 29 (2006), 4; 889-902. doi: 10.3892/ijo.29.4.889

Podaci o odgovornosti

Becker, Kerstin ; Pancoska, Petr ; Concin, Nicole ; Vanden Heuvel, Kelly ; Slade, Neda ; Fischer, Margaret ; Chalas, Eva ; Moll, Ute, M.

engleski

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

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.

p73 ; p53 ; gynecological cancer

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Podaci o izdanju

29 (4)

2006.

889-902

objavljeno

1019-6439

1791-2423

10.3892/ijo.29.4.889

Povezanost rada

Temeljne medicinske znanosti

Poveznice
Indeksiranost