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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China.
Zhenqiang
Z
Sun
Department of Epidemiology and Health Statistics, School of Public Health, Central South University, Changsha, Hunan, China; Department of Infection Control, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China.
Ruiwei
R
Xu
Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer and Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiayu
X
Li
Hunan Key Laboratory of Nonresolving Inflammation and Cancer and Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Weiguo
W
Ren
Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
Chunlin
C
Ou
Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China.
Qisan
Q
Wang
Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
Han
H
Zhang
Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
Xuemei
X
Zhang
Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer and Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China; Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, China.
Jian
J
Ma
Department of Gastrointestinal Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi, Xinjiang, China.
Haijiang
H
Wang
Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer and Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China; Hunan Provincial Tumor Hospital and The Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan, China.
Guiyuan
G
Li
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000401:mortality*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D017594:Publication Bias; D016019:Survival Analysis; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human