Aberrant upregulation of 14-3-3ơ expression serves as an inferior prognostic biomarker for gastric cancer
- Equal contributors
1 Department of Hematology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
2 Department of Pathology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
3 State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, China
4 Department of Pathology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
BMC Cancer 2011, 11:397 doi:10.1186/1471-2407-11-397Published: 20 September 2011
14-3-3ơ is an intracellular, phosphoserine binding protein and proposed to be involved in tumorigenesis. However, the expression dynamics of 14-3-3ơ and its clinicopathological/prognostic significance in human tumors are still controversial.
The method of immunohistochemistry (IHC) and Western blot were utilized to examine the protein expression of 14-3-3ơ in gastric cancer and paired normal adjacent gastric mucosal tissues. Receive operating characteristic (ROC) curve analysis was employed to determine a cutoff score for 14-3-3ơ expression in a training set (n = 66). For validation, the ROC-derived cutoff score was subjected to analysis of the association of 14-3-3ơ expression with patient outcome and clinical characteristics in a testing set (n = 86) and overall patients (n = 152).
The expression frequency and expression levels of 14-3-3ơ were significantly higher in gastric cancer than in normal gastric mucosal tissues. Correlation analysis demonstrated that high expression of 14-3-3ơ in gastric cancer was significantly correlated with clinical stage and tumor invasion. Furthermore, in the testing set and overall patients, Kaplan-Meier analysis showed that elevated 14-3-3ơ expression predicted poorer overall survival (OS) and progression-free survival (PFS). Importantly, high 14-3-3ơ expression was also associated with shortened survival time in stage III and stage IV gastric cancer patients. Multivariate analyses revealed that 14-3-3ơ expression was an independent prognostic parameter in gastric cancer.
These findings provide evidence that high expression of 14-3-3ơ may be important in the tumor progression and servers as an independent molecular marker for poor prognosis of gastric cancer. Thus, overexpression of 14-3-3ơ identifies patients at high risk and is a novel therapeutic molecular target for this tumor.