Woojin Jeong1, Sang-Bae Kim2,3, Bo Hwa Sohn2,3, Yun-Yong Park2,3, Eun Sung Park4, Sang Cheol Kim5, Sung Soo Kim6, Randy L Johnson7, Michael Birrer8, David S L Bowtell9, Gordon B Mills2,3, Anil Sood10,11,12, Ju-Seog Lee2,3,6. 1. Department of Life Sciences, Division of Life and Pharmaceutical Sciences, Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul, Korea. 2. Department of Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. 3. Kleberg Center for Molecular Markers, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. 4. Institute for Medical Convergence, Yonsei University College of Medicine, Seoul, Korea. 5. Samsung Genome Institute, Samsung Medical Center, Gangnam-Gu, Seoul, Korea. 6. Department of Biochemistry and Molecular Biology, Medical Research Center and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Korea. 7. Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. 8. Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA. 9. Peter MacCallum Cancer Center, Melbourne, Victoria, Australia. 10. Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. 11. Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. 12. Center for RNA Interference and Non-coding RNA, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
Abstract
AIM: 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. MATERIALS AND 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. CONCLUSION: 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.
RCT Entities:
AIM: 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. MATERIALS AND 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 cancerYAP1 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. CONCLUSION: 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.
Entities:
Keywords:
DNA microarrays; YAP1; ovarian cancer; prognosis; taxane
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