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. We performed a meta-analysis based on individual study outcomes to more 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 the possibility of publication bias through a funnel plot and identified the heterogeneity by I(2) statistics. Results. Eleven eligible studies were analyzed for PTEN, 5 for PI3K, and 11 for pAkt. High PI3K and pAkt expression was associated with poor overall survival (OS; pooled adjusted hazard ratio [HR] = 1.44, 95% CI, 1.08-1.91 for PI3K; HR = 1.60, 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 = 1.24, 95% CI, 1.10-1.39; pooled adjusted HR = 1.65, 95% CI, 1.07-2.55). Conclusion. Published studies suggest that high pAkt expression is significantly associated with poor OS 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.
摘要
简介 PTEN/PI3K/Akt 信号转导通路在介导凋亡、代谢、细胞增殖和细胞生长方面发挥着关键作用，在很多癌症中往往都存在失调。但是，关于这个通路对上皮性卵巢癌 (EOC) 的预后影响，目前仍无一致结论。我们对各个研究结局指标进行了一项荟萃分析，以便更确切地评估它在 EOC 患者中的临床意义。
方法 我们搜索了 1990 年 1 月 1 日至 2013 年 3 月 1 日期间发表的所有可能与此有关的研究，这些研究评估了 PTEN、PI3K 和 Akt 状态与 EOC 生存期之间的关联。荟萃分析的模型酌情采用了固定效应模型或随机效应模型。我们通过一个漏斗曲线评估了发表偏倚的概率，并通过 I2 统计值确定了异质性。
结果 我们为 PTEN 分析了 11 项合格研究，为 PI3K 分析了 5 项，为 pAkt 分析了 11 项。PI3K 和 pAkt 的高表达通常伴随较低的总生存期（OS；PI3K 的汇总校正后风险比 [HR] = 1.44, 95% CI, 1.08–1.91；pAkt 的 HR = 1.60, 95% CI, 1.26–2.04）。此外，单一变量和多变量估计值的荟萃分析均显示，只有 pAkt 的高表达与无进展生存期不佳存在显著关联（PFS；汇总非校正 HR = 1.24 CI, 95% CI, 1.10–1.39；汇总校正后 HR = 1.65, 95% CI, 1.07–2.55）。
结论 已发表研究表明，pAkt 的高表达与 EOC 患者的 OS 和 PFS 不佳存在显著关联，但现有证据不足以支持将 PTEN、PI3K 或 Akt 作为 EOC 的预后预测因子应用于临床。The Oncologist 2014;19:528–535
Keywords: Epithelial ovarian cancer; Meta-analysis; Overall survival; PTEN/PI3K/Akt; Progression-free survival.