Reduced Expression of Transcription Factor AP-2α Is Associated with Gastric Adenocarcinoma Prognosis

Background: This study aims to investigate the expression and prognostic significance of activator protein 2 alpha (AP-2 alpha) in gastric adenocarcinoma. Methodology/Principal Findings: AP-2 alpha expression was analyzed using real-time quantitative PCR (RT-qPCR), western blotting, and immunohistochemical staining methods on tissue samples from a consecutive series of 481 gastric adenocarcinoma patients who underwent resections between 2003 and 2006. The relationship between AP-2 alpha expression, clinicopathological factors, and patient survival was investigated. RT-qPCR results showed that the expression of AP-2 alpha mRNA was reduced in tumor tissue samples, compared with expression in matched adjacent non-tumor tissue samples (P = 0.009); this finding was confirmed by western blotting analysis (P = 0.012). Immunohistochemical staining data indicated that AP-2 alpha expression was significantly decreased in 196 of 481 (40.7%) gastric adenocarcinoma cases; reduced AP-2 alpha expression was also observed in patients with poorly differentiated tumors (P = 0.001) and total gastric carcinomas (P = 0.002), as well as in patients who underwent palliative tumor resection (P = 0.004). Additionally, reduced expression of AP-2 alpha was more commonly observed in tumors that were staged as T4a/b (P = 0.018), N3 (P = 0.006), and M1 (P = 0.008). Kaplan-Meier survival curves revealed that reduced expression of AP-2 alpha was associated with poor prognosis in gastric adenocarcinoma patients (P<0.001). Multivariate Cox analysis identified AP-2 alpha expression as an independent prognostic factor for overall survival (HR = 1.512, 95% CI = 1.127-2.029, P = 0.006). Conclusions/Significance: Our data suggest that AP-2 alpha plays an important role in tumor progression and that reduced AP-2 alpha expression independently predicts an unfavorable prognosis in gastric adenocarcinoma patients.