Abstract
BackgroundYes-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.MethodsA 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.ResultsA 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).ConclusionBoth 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.
Highlights
The Hippo pathway is an important signaling pathway controlling organ size and regulating cell proliferation and apoptosis, and dysfunction of this pathway often contributes to development and tumorigenesis [1, 2]
Both overall and nuclear Yes-associated protein 1 (YAP1) overexpression are intimately associated with adverse overall survival (OS) and disease free survival (DFS) in numerous cancers, suggesting that YAP1 may act as a potential therapeutic targets of these malignancies in the future
YAP1 has often been described as an oncogene, which usually leads to a poor prognosis
Summary
The Hippo pathway is an important signaling pathway controlling organ size and regulating cell proliferation and apoptosis, and dysfunction of this pathway often contributes to development and tumorigenesis [1, 2]. YAP1 is a downstream target of the Hippo pathway and plays a role as a transcription co-activator [3]. Restriction of YAP1 transcriptional activity is the principal mechanism of growth and tumor suppression by the Hippo pathway. Many previous studies have reported elevated YAP1 protein levels in various types of cancer, such as colorectal cancer (CRC), gastric cancer, human hepatocellular carcinoma (HCC) etc. 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. These studies were limited by the small samples size and the findings were inconsistent among them. A meta-analysis was conducted to assess the association between YAP1 and malignancies
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