The Role of the PTEN/PI3K/Akt Pathway on Prognosis in Epithelial Ovarian Cancer: A Meta-Analysis

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)isstillinconsistent.Weperformedameta-analysis basedonindividualstudyoutcomestomorepreciselyevaluate 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 investigatedthepossibilityofpublicationbiasthroughafunnel plot and identified the heterogeneity by I 2 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,1.08–1.91forPI3K;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 HR 5 1.24, 95% CI, 1.10–1.39; pooled adjusted HR 51.65, 95% CI, 1.07–2.55). Conclusion. PublishedstudiessuggestthathighpAktexpression issignificantlyassociatedwithpoorOSandPFSinEOCpatients, but currently available evidence is insufficient to recommend that PTEN, PI3K, or Akt be used as prognostic predictors in EOC in clinical practice.The Oncologist2014;19:528–535 Implications for Practice: We performed a meta-analysis based on individual study outcomes to evaluate the clinical significanceofthePTEN/PI3K/Aktsignalingpathwayinepithelialovariancancer(EOC)patients.Wefoundthathighexpression of activated Akt (pAkt) was significantly associated with poor survival in EOC patients, but currently available evidence is insufficienttorecommendPTEN, PI3K,orAkttobeusedas aprognostic predictor inEOCinclinicalpractice.Thisstudyis both important and immediately clinically relevant because currently, in spite of tremendous efforts in the field of biomarker discoveryanddevelopment,forEOC,molecularassistsintheclinicopathologicandprognosistoolboxarelacking.Furthermore, identification of more accurate and more effective detection techniques and unified evaluation criteria to mandate homogeneous data collection is urgently needed.