Nuclear localization of 14-3-3epsilon inversely correlates with poor long-term survival of patients with colorectal cancer

Background 14-3-3 epsilon regulates diverse biological processes and plays a significant role in the formation of malignant tumors. However, the localization and clinical significance of 14-3-3 epsilon in colorectal cancer (CRC) have not been elucidated. Methods We investigated 14-3-3 epsilon expression and its prognostic significance in CRC. CRC surgical samples were taken from 137 clinicopathologically characterized CRC cases. 14-3-3 epsilon expression was tested by immunohistochemical assay. Separate Western blot of nuclear and cytosol preparations confirmed nuclear localization of 14-3-3 epsilon protein. Results Nuclear expression of 14-3-3 epsilon was observed in 76.9% of normal colorectal tissue and 78.8% of all CRC samples. Statistical analysis showed that there was significant difference of nuclear 14-3-3 epsilon expression in patients categorized according to lymph node metastasis. A trend was identified between decreasing nuclear 14-3-3 epsilon expression in CRC and worsening clinical prognosis. Multivariate analysis showed that loss of nuclear 14-3-3 epsilon expression was an independent prognostic indicator for patient's survival. Conclusions The current data provide evidence that 14-3-3 epsilon is not exclusively a cytosolic protein, but is also detectable within the nucleus. Our results suggest that nuclear 14-3-3 epsilon as a suppressor may serve as important biomarker of tumor metastasis. Loss of nuclear 14-3-3 epsilon is closely associated with poor overall survival in CRC patients. J. Surg. Oncol. 2012; 106:224-231. (c) 2011 Wiley Periodicals, Inc.