Notch1 Expression, Which Is Related to p65 Status, Is an Independent Predictor of Prognosis in Colorectal Cancer

Purpose: Notch1 has been proven to be aberrantly expressed in colorectal cancer and related to tumor differentiation status. However, few previous studies concentrated on the predictive role of Notch1 expression on the overall survival of patients with colorectal cancer. This study explored expression of Notch1 and its relationship with p65 and prognosis in colorectal cancer. Experimental Design: Two independent study cohorts were involved in the present study. Clinical specimens from 941 eligible patients were constructed into tissue microarrays. The expression of Notch1 and p65 protein was investigated by immunohistochemistry. Results: Statistically significant positive correlations were found between protein expression of Notch1 and p65 in both retrospective and prospective study cohorts. Patients with higher Notch1 expression showed a trend of having shorter survival time, whereas patients with lower Notch1 expression had better survival in both study cohorts. In multivariate analysis, Notch1 expression was proven to be an independent predictor of prognosis. Moreover, the prognostic value of Notch1 might differ according to p65 status. Conclusions: Notch1 is an independent predictor of prognosis for patients with colorectal cancer. In addition, the predictive role of Notch1 on clinical outcome might be modified by p65 status, suggesting that targeting Notch1 and nuclear factor kappa B (NF-kappa B) might be a promising strategy for colorectal cancer treatment. Clin Cancer Res; 17(17); 5686-94. (C)2011 AACR.