Cancer : A Meta-Analysis The Role of the PTEN / PI 3 K / Akt Pathway on Prognosis in Epithelial Ovarian

Introduction.The PTEN/PI3K/Akt signaling pathway, a key player in mediating apoptosis, metabolism, cell proliferation, and cell growth, is frequently dysregulated in many cancers. However, the pathway’s prognostic impact in epithelial ovarian cancer (EOC) is still inconsistent.Weperformed ameta-analysis based on individual study outcomes tomore precisely evaluate its clinical significance in EOC patients. Methods.We searched all potentially relevant studies published between January 1, 1990, and March 1, 2013, that assessed the association between PTEN, PI3K, and Akt status and survival in EOC. Meta-analysis was performed using a fixed-effect or random-effects model as appropriate. We investigated thepossibilityofpublicationbias througha funnel plot and identified the heterogeneity by I statistics. Results. EleveneligiblestudieswereanalyzedforPTEN,5forPI3K, and 11 for pAkt. High PI3K and pAkt expression was associated with poor overall survival (OS; pooled adjusted hazard ratio [HR] 51.44, 95%CI, 1.08–1.91 for PI3K; HR51.60, 95%CI, 1.26–2.04 for pAkt). In addition, both the meta-analyses of univariate and multivariate estimates showed that only high pAkt expression was significantly associated with poor progression-free survival (PFS; pooled unadjusted HR5 1.24, 95% CI, 1.10–1.39; pooled adjusted HR5 1.65, 95% CI, 1.07–2.55). Conclusion. PublishedstudiessuggestthathighpAktexpression is significantly associatedwith poorOS and PFS in EOC patients, but currently available evidence is insufficient to recommend that PTEN, PI3K, or Akt be used as prognostic predictors in EOC in clinical practice. The Oncologist 2014;19:528–535 Implications for Practice: We performed a meta-analysis based on individual study outcomes to evaluate the clinical significance of the PTEN/PI3K/Akt signaling pathway in epithelial ovarian cancer (EOC) patients.We found that high expression of activated Akt (pAkt) was significantly associated with poor survival in EOC patients, but currently available evidence is insufficient to recommend PTEN, PI3K, or Akt to be used as a prognostic predictor in EOC in clinical practice.This study is both important and immediately clinically relevant because currently, in spite of tremendous efforts in the field of biomarker discovery anddevelopment, for EOC,molecular assists in the clinicopathologic andprognosis toolboxare lacking. Furthermore, identification of more accurate and more effective detection techniques and unified evaluation criteria to mandate homogeneous data collection is urgently needed.