Prognostic Value of Yes-Associated Protein 1 (YAP1) in Various Cancers: A Meta-Analysis

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.

PIK3CA mutations as prognostic factor in squamous cell lung carcinoma

“…YAP has recently become an interesting area for oncology research since this cotranscription factor is seen as a mechanism of drug resistance in a variety of cell types including breast and lung cancers (Kim et al, 2015a, Steinhardt et al, 2008. Survival studies have shown a correlation between YAP nuclear localization and poor prognosis in patients diagnosed with lung ACs (Kim et al, 2015b) along with a meta analysis studying various cancers highlighting furthering YAP's involvement in prognosis (Sun et al, 2015). Molecular studies have also shown YAP to regulate AXL and PD-L1 expression (Boin et al, 2014.…”

Searching for the link; mechanisms underlying liver regeneration and recurrence of colorectal liver metastasis post partial hepatectomy

“…A recent review has highlighted the bilateral roles of Yap, as both a tumor suppressor and an oncogene in CRC. Nuclear Yap overexpression has been observed in various cancers, including CRC, and correlates inversely with OS and DFS . Furthermore, Yap is associated with EMT, a process which contributes to cancer invasiveness and metastasis …”

“…Nuclear Yap overexpression has been observed in various cancers, including CRC, and correlates inversely with OS and DFS. 44 Furthermore, Yap is associated with EMT, a process which contributes to cancer invasiveness and metastasis. 45 Processes involved in liver regeneration, tumorigenesis, and tumor progression.…”

YAP and the Hippo pathway in pediatric cancer

“…Many previous studies have reported elevated YAP protein levels in various types of cancer, such as colorectal, gastric, and human hepatocellular carcinoma. 12,13 In this context, YAP is often described as an oncogene and its increased expression in cancers correlates with poor prognosis. For example, increased YAP expression is associated with high clinical stage and short overall survival in colorectal and ovarian cancer.…”

“…For example, increased YAP expression is associated with high clinical stage and short overall survival in colorectal and ovarian cancer. 13,14 In other contexts, YAP functions as a tumor suppressor while inducing cell apoptosis. This alternate function of YAP has been noted in few morphologic studies of breast and prostate cancer, which have shown that YAP expression is lost in the tumor cells and retained in normal tissues.…”