14-3-3σ expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients

Alexander Perathoner, Daniela Pirkebner, Gerald Brandacher, Gilbert Spizzo, Sylvia Stadlmann, Peter Obrist, Raimund Margreiter, Albert Amberger

Research output: Contribution to journalArticle

Abstract

Purpose: 14-3-3σ is an intracellular, dimeric, phosphoserine binding protein that is expressed in epithelial cells and involved in cancer development. In this study was examined the expression of 14-3-3σ and evaluated its clinical significance in colorectal carcinoma. Experimental Design: Expression of 14-3-3σ was analyzed by Western blot in nine colorectal carcinoma cell lines, eight paired colorectal carcinoma tissues, and normal mucosas. Immunohistochemistry was used to evaluate expression of 14-3-3σ in tissues of 121 colorectal carcinoma patients and to correlate it with clinical parameters. Results: Western blot analysis of colorectal carcinoma cell lines and tissues revealed strong 14-3-3σ expression in four of eight cell lines and 14-3-3σ overexpression in carcinoma compared with normal mucosa in six of eight colorectal carcinoma tissue pairs. Immunohistochemical analysis revealed 14-3-3σ overexpression in 38.8% of colorectal carcinoma samples. Furthermore, highly positive immunoreactivity was significantly correlated with tumor differentiation (P < 0.001) and pT stage (P < 0.003). In Kaplan-Meier analysis, 14-3-3σ overexpression was associated with a significantly decreased survival time compared with negatively stained or low stained cases (P < 0.0096). In multiveriate regresion analysis, 14-3-3σ expression emerged as a significant independent parameter (P < 0.037). Conclusions: These results provide evidence that 14-3-3σ expression increases during carcinoma progression in a subset of colorectal carcinoma. The overexpression of this antigen identifies patients at high risk. It is tempting to suggest that 14-3-3σ overexpression either promotes tumor proliferation and/or prevents apoptotic signal transduction in colorectal carcinomas. Thus, targeting 14-3-3σ might be a new therapeutic strategy in colorectoral carcinoma.

Original languageEnglish (US)
Pages (from-to)3274-3279
Number of pages6
JournalClinical Cancer Research
Volume11
Issue number9
DOIs
StatePublished - May 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Perathoner, A., Pirkebner, D., Brandacher, G., Spizzo, G., Stadlmann, S., Obrist, P., Margreiter, R., & Amberger, A. (2005). 14-3-3σ expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients. Clinical Cancer Research, 11(9), 3274-3279. https://doi.org/10.1158/1078-0432.CCR-04-2207