title: Activation of YAP1 is associated with poor prognosis and response to taxanes in ovarian cancer.
abstract: OBJECTIVE
  We aimed to investigate the clinical significance of the activation of Yes-Associated Protein 1 (YAP1), a key downstream effector of Hippo tumor-suppressor pathway, in ovarian cancer.
  
  
  METHODS
  A gene expression signature reflecting activation of YAP1 was developed from gene expression data of 267 samples from patients with ovarian cancer. A refined ovarian cancer YAP1 signature was validated in an independent ovarian cancer cohort (n=185). Associations between the YAP1 signature and prognosis were assessed using Kaplan-Meier plots, the log-rank test, and a Cox proportional hazards model.
  
  
  RESULTS
  We identified a 612-gene expression signature reflecting YAP1 activation in ovarian cancer. In multivariate analysis, the signature was an independent predictor of overall survival (hazard ratio=1.66; 95% confidence interval=1.1 to 2.53; p=0.01). In subset analysis, the signature identified patients likely to benefit from taxane-based adjuvant chemotherapy.
  
  
  CONCLUSIONS
  Activation of YAP1 is significantly associated with prognosis and the YAP1 signature can predict response to taxane-based adjuvant chemotherapy in patients with ovarian cancer.
authors: Department of Life Sciences, Division of Life and Pharmaceutical Sciences, Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul, Korea.
authors: Woojin
authors: W
authors: Jeong
authors: Department of Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.|Kleberg Center for Molecular Markers, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Sang-Bae
authors: SB
authors: Kim
authors: Department of Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.|Kleberg Center for Molecular Markers, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Bo Hwa
authors: BH
authors: Sohn
authors: Department of Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.|Kleberg Center for Molecular Markers, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Yun-Yong
authors: YY
authors: Park
authors: Institute for Medical Convergence, Yonsei University College of Medicine, Seoul, Korea.
authors: Eun Sung
authors: ES
authors: Park
authors: Samsung Genome Institute, Samsung Medical Center, Gangnam-Gu, Seoul, Korea.
authors: Sang Cheol
authors: SC
authors: Kim
authors: Department of Biochemistry and Molecular Biology, Medical Research Center and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea.
authors: Sung Soo
authors: SS
authors: Kim
authors: Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Randy L
authors: RL
authors: Johnson
authors: Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors: Michael
authors: M
authors: Birrer
authors: Peter MacCallum Cancer Center, Melbourne, Victoria, Australia.
authors: David S L
authors: DSL
authors: Bowtell
authors: Department of Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.|Kleberg Center for Molecular Markers, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Gordon B
authors: GB
authors: Mills
authors: Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.|Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.|Center for RNA Interference and Non-coding RNA, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors: Anil
authors: A
authors: Sood
authors: Department of Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.|Kleberg Center for Molecular Markers, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.|Department of Biochemistry and Molecular Biology, Medical Research Center and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea.
authors: Ju-Seog
authors: JS
authors: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016000:Cluster Analysis; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D000090683:Hippo Signaling Pathway; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction; D043823:Taxoids / Q000008:administration & dosage; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D043823:Taxoids; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: DNA microarrays; YAP1; ovarian cancer; prognosis; taxane