Prognostic Value of Yes-Associated Protein 1 (YAP1) in Various Cancers: A Meta-Analysis.
Prognostic Value of Yes-Associated Protein 1 (YAP1) in Various Cancers: A Meta-Analysis.
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Yes 相关蛋白 1 (YAP1) 在各种癌症中的预后价值：荟萃分析。
DOI：
10.1371/journal.pone.0135119
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
Sun Z;Xu R;Li X;Ren W;Ou C;Wang Q;Zhang H;Zhang X;Ma J;Wang H;Li G
YAP 1是Hippo信号通路的一个效应子，在哺乳动物器官大小、细胞增殖和肿瘤生长等方面起着重要作用。许多先前的研究探索了YAP 1与各种癌症之间的关系。然而，这些研究受到样本量小的限制，并且它们之间的结果不一致。因此，进行荟萃分析以评估YAP 1与恶性肿瘤之间的关联。对PubMed、Corchane Library、Web of Knowledge、EMBASE和CBM光盘数据库中从开始到2014年8月1日的合格研究进行了系统性文献检索。异质性分析后，在STATA 10.0中使用固定和随机效应模型估计合并harzad比（HR）及其95%置信区间（95%CI）。采用Meta回归分析、亚组分析和敏感性分析等方法探讨异质性的潜在来源，并评价结果的稳健性。采用Egger检验和漏斗图评估发表偏倚。荟萃分析共分析了2009年至2014年的21篇独特文章，包括2983例患者。在20项研究（包括2067例患者）中评估了YAP 1表达与总生存时间（OS）的相关性。YAP 1阳性者OS较差（HR = 1.826; 95%CI = 1.465-2.275; p <0.002）。为了评估无病生存时间（DFS），分析了10项研究（1139例患者）。YAP 1阳性者DFS较差（HR = 2.114; 95%CI = 1.406-3.179; p <0.001）。亚组分析显示，对于恶性肿瘤患者，核YAP 1阳性（HR = 1.390，95% CI：0.810-2.400，p = 0.729）和上调的总体YAP 1（HR = 2.237，95% CI：1.548-3.232，p <0.001）均具有较差的OS。类似地，阳性核YAP 1（HR = 3.733，95%CI：1.469-9.483，p = 0.001）和上调总体YAP 1（HR = 1.481，95%CI：1.163-1.886，p = 0.554）均显示较差的DFS。泌尿生殖系统肿瘤患者的OS最差（HR = 2.133，95%CI：1.549-2.937，p = 0.020）。消化系统恶性肿瘤对DFS的影响最大（HR = 1.879，95% CI：1.537-2.297，p <0.001）。在许多癌症中，总体和核YAP 1过表达与不良OS和DFS密切相关，这表明YAP 1可能在未来作为这些恶性肿瘤的潜在治疗靶点。
Yes-associated protein 1 (YAP1) is an effector of Hippo pathway, which is critical for regulating organ size, cell proliferation and tumor growth in mammals. Many previous studies have explored the relationship between YAP1 and various types of cancer. However, these studies were limited by the small samples size and the findings were inconsistent among them. Therefore, a meta-analysis was conducted to assess the association between YAP1 and malignancies. A systematic literature search was conducted for eligible studies in the PubMed, Corchane Library, Web of Knowledge, EMBASE and CBM disc databases from inception to August 1st 2014. After heterogeneity analysis, pooled harzad ratio (HR) with 95% confidence interval (95%CI) using both fixed and random effect models were estimated in STATA 10.0. Meta regression analysis, subgroup analysis and sensitivity analysis were performed to explore the potential sources of heterogeneity and to evaluate the robustness of the result. Publication bias was assessed by Egger’s test and funnel plot. A total of 21 unique articles from 2009 to 2014, comprising 2983 patients, were analyzed in the meta-analysis. The association of YAP1 expression and overall survival time (OS) was evaluated in 20 studies including 2067 patients. Positive YAP1 showed poorer OS (HR = 1.826; 95% CI = 1.465–2.275; p <0.002). For evaluating disease-free survival time (DFS), 10 studies with 1139 patients were analyzed. Positive YAP1 indicated worse DFS (HR = 2.114; 95%CI = 1.406–3.179; p <0.001). Subgroup analysis showed that both positive nuclear YAP1 (HR = 1.390, 95% CI: 0.810–2.400, p = 0.729) and up-regulation overall YAP1 (HR = 2.237, 95% CI: 1.548–3.232, p <0.001) had poorer OS for patients with malignancies. Similarly, both positive nuclear YAP1 (HR = 3.733, 95% CI: 1.469–9.483, p = 0.001) and up-regulation overall YAP1 (HR = 1.481, 95% CI: 1.163–1.886, p = 0.554) showed worse DFS. The patients with urogenital system cancer had the poorest OS (HR = 2.133, 95% CI: 1.549–2.937, p = 0.020). The patients with alimentary system cancer had the most significant impact on DFS (HR = 1.879, 95% CI: 1.537–2.297, p <0.001). Both overall and nuclear YAP1 overexpression are intimately associated with adverse OS and DFS in numerous cancers, suggesting that YAP1 may act as a potential therapeutic targets of these malignancies in the future.