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

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.