Prognostic gene expression signature for high-grade serous ovarian cancer
Millstein, Joshua (University of Southern California)
Budden, Timothy (The University of Manchester)
Goode, Ellen L. (Mayo Clinic)
Anglesio, Michael (University of British Columbia)
Talhouk, Aline (University of British Columbia)
Intermaggio, Maria Paola (University of NSW Sydney)
Leong, Hueisan (Peter MacCallum Cancer Center)
Chen, Stephanie S. (Cedars-Sinai Medical Center)
Elatre, Wafaa A. (University of Southern California)
Gilks, Cyril Blake (University of British Columbia)
Nazeran, Tayyebeh M. (University of British Columbia)
Volchek, Mila (Royal Women's Hospital)
Bentley, Rex C. (Duke University Hospital)
Wang, Chen (Mayo Clinic)
Chiu, Derek S. (University of British Columbia)
Kommoss, Stefan (Tuebingen University Hospital)
Leung, Samuel C. Y. (University of British Columbia)
Senz, Janine (University of British Columbia)
Lum, Amy (University of British Columbia)
Chow, Veronica (University of British Columbia)
Sudderuddin, Hanwei (University of British Columbia)
Mackenzie, Robertson (University of British Columbia)
George, Joshy (The Jackson Laboratory for Genomic Medicine)
Fereday, Sian (University of Melbourne)
Hendley, Joy (University of Melbourne)
Traficante, Nadia (University of Melbourne)
Steed, Helen (Royal Alexandra Hospital)
Koziak, Jennifer M. (Alberta Health Services-Cancer Care)
Köbel, Martin (Foothills Medical Center)
McNeish, Iain (University of Glasgow)
Goranova, Teodora Evgenieva (University of Cambridge)
Ennis, Darren P. (University of Glasgow)
Macintyre, Geoff (University of Cambridge)
Silva De Silva, D. (University of Cambridge)
Ramon y Cajal, Teresa (Institut d'Investigació Biomèdica Sant Pau)
García Donas, J. (HM Hospitales D Centro Integral Oncológico HM Clara Campal)
Hernando, Susana (Hospital Universitario Funcacion Alcorcon)
Rodriguez, Gustavo C. (University of Chicago)
Cushing-Haugen, Kara L. (Fred Hutchinson Cancer Research Center)
Harris, Holly Ruth (University of Washington)
Greene, Casey S. (University of Pennsylvania)
Zelaya, René A. (Geisel School of Medicine at Dartmouth)
Behrens, Sabine (German Cancer Research Center (DKFZ))
Fortner, Renée T. (German Cancer Research Center (DKFZ))
Sinn, Hans-Peter (Heidelberg University Hospital (Alemanya))
Herpel, Esther (University Hospital and German Cancer Research Center)
Lester, Jenny (Cedars-Sinai Medical Center)
Lubinski, Jan (Pomeranian Medical University)
Oszurek, Oleg (Pomeranian Medical University)
Tołoczko, Aleksandra D. (Pomeranian Medical University)
Cybulski, Cezary (Pomeranian Medical University)
Menkiszak, Janusz Leszek (Pomeranian Medical University)
Pearce, Celeste Leigh (University of Southern California Norris Comprehensive Cancer Center)
Pike, Malcolm C. (Memorial Sloan-Kettering Cancer Center (Nova York, Estats Units d'Amèrica))
Tseng, Chiuchen Cheng (University of Southern California)
Alsop, Jennifer (University of Cambridge)
Rhenius, Valerie (University of Cambridge)
Song, Hongan (University of Cambridge)
Jimenez-Liñan, Mercedes (Addenbrooke's Hospital NHS Trust)
Piskorz, Anna M. (University of Cambridge)
Gentry-Maharaj, Aleksandra (University College London)
Karpinskyj, Chloe (University College London)
Widschwendter, M. (University College London)
Singh, Naveena K. (Barts Health National Health Service Trust)
Kennedy, Catherine J. (Westmead Hospital)
Harnett, Paul R. (University of Sidney)
Gao, Bo (Westmead Hospital)
Johnatty, Sharon E. (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Sayer, Robyn A. (Westmead Hospital)
Boros, Jessica (Westmead Hospital)
Winham, Stacey J. (Mayo Clinic)
Keeney, Gary L. (Mayo Clinic)
Kaufmann, Scott H. (Mayo Clinic)
Larson, Melissa C. (Mayo Clinic)
Luk, Hugh W. (University of Hawaii Cancer Center)
Hernandez, Brenda Y. (University of Hawaii Cancer Center)
Thompson, Pamela J. (Cedars-Sinai Medical Center)
Wilkens, Lynne Ross (University of Hawaii Cancer Center)
Carney, Michael E. (University of Hawaii)
Trabert, Britton (National Cancer Institute)
Lissowska, Jolanta (M Sklodowska Curie National Research Institute of Oncology)
Brinton, Louise Annette (National Cancer Institute)
Sherman, Mark E. (Mayo Clinic College of Medicine)
Bodelón, Clara (National Cancer Institute)
Hinsley, Samantha (University of Glasgow)
Lewsley, Liz Anne (University of Glasgow)
Glasspool, Rosalind M. (University of Glasgow)
Banerjee, Susana (The Royal Marsden NHS Foundation Trust and Institute of Cancer Research)
Stronach, Euan A. (Imperial College London)
Haluska, Paul J. (Mayo Clinic)
Ray-Coquard, Isabelle Laure (Centre Leon Berard and University Claude Bernard Lyon 1)
Mahner, Sven (LMU Munich)
Winterhoff, Boris J. N. (University of Minnesota)
Slamon, Dennis J. (University of California at Los Angeles)
Levine, Douglas A. (NYU Langone Medical Center)
Kelemen, Linda E. (Medical University of South Carolina)
Benitez, Javier J. (Centro Nacional de Investigaciones Oncológicas)
Chang-Claude, J. (University Medical Center Hamburg-Eppendorf)
Gronwald, Jacek (Pomeranian Medical University)
Wu, Anna H. (University of Southern California)
Menon, Usha (MRC University College London)
Goodman, Marc T. (Cedars-Sinai Medical Center)
Schildkraut, Joellen M. (Emory University)
Wentzensen, Nicolas A. (National Cancer Institute)
Brown, Robert (Imperial College London)
Berchuck, Andrew (Duke University Hospital)
Gayther, Simon A. (Cedars-Sinai Medical Center)
García, M. J. (Centro de Investigación Biomédica en Red de Enfermedades Raras)
Henderson, Michelle J. (University of NSW Sydney)
Rossing, Mary Anne (University of Washington)
Beeghly-Fadiel, Alicia (Vanderbilt University School of Medicine)
Fasching, Peter Andreas (Friedrich-Alexander-University Erlangen-Nuremberg)
Orsulic, Sandra (Cedars-Sinai Medical Center)
Karlan, Beth Y. (Cedars-Sinai Medical Center)
Konecny, Gottfried Ewald (University of California at Los Angeles)
Huntsman, David G. (BC Cancer Research Centre)
Brenton, James D. (University of Cambridge)
Doherty, Jennifer Anne (University of Utah)
Pharoah, Paul D. P. (University of Cambridge)
Ramus, Susan (University of NSW Sydney)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is ∼4 years, yet survival varies widely between patients. There are no well-established, gene expression signatures associated with prognosis. The aim of this study was to develop a robust prognostic signature for OS in patients with HGSOC. Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, was measured using NanoString technology from formalin-fixed paraffin-embedded tumour tissue collected from 3769 women with HGSOC from multiple studies. Elastic net regularization for survival analysis was applied to develop a prognostic model for 5-year OS, trained on 2702 tumours from 15 studies and evaluated on an independent set of 1067 tumours from six studies. Expression levels of 276 genes were associated with OS (false discovery rate < 0. 05) in covariate-adjusted single-gene analyses. The top five genes were TAP1, ZFHX4, CXCL9, FBN1 and PTGER3 (P < 0. 001). The best performing prognostic signature included 101 genes enriched in pathways with treatment implications. Each gain of one standard deviation in the gene expression score conferred a greater than twofold increase in risk of death [hazard ratio (HR) 2. 35, 95% confidence interval (CI) 2. 02-2. 71; P < 0. 001]. Median survival [HR (95% CI)] by gene expression score quintile was 9. 5 (8. 3 to -), 5. 4 (4. 6-7. 0), 3. 8 (3. 3-4. 6), 3. 2 (2. 9-3. 7) and 2. 3 (2. 1-2. 6) years. The OTTA-SPOT (Ovarian Tumor Tissue Analysis consortium - Stratified Prognosis of Ovarian Tumours) gene expression signature may improve risk stratification in clinical trials by identifying patients who are least likely to achieve 5-year survival. The identified novel genes associated with the outcome may also yield opportunities for the development of targeted therapeutic approaches.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Formalin-fixed paraffin-embedded ; Gene expression ; High-grade serous ovarian cancer ; Overall survival ; Prognosis
Publicat a:	Annals of oncology, Vol. 31 Núm. 9 (01 2020) , p. 1240-1250, ISSN 1569-8041

DOI: 10.1016/j.annonc.2020.05.019
PMID: 32473302

11 p, 1.4 MB

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