Meta-Analysis

. 2020 Sep;31(9):1240-1250.

doi: 10.1016/j.annonc.2020.05.019. Epub 2020 May 28.

Prognostic gene expression signature for high-grade serous ovarian cancer

J Millstein¹, T Budden², E L Goode³, M S Anglesio⁴, A Talhouk⁵, M P Intermaggio⁶, H S Leong⁷, S Chen⁸, W Elatre⁹, B Gilks¹⁰, T Nazeran¹¹, M Volchek¹², R C Bentley¹³, C Wang¹⁴, D S Chiu¹¹, S Kommoss¹⁵, S C Y Leung¹¹, J Senz¹⁰, A Lum¹¹, V Chow¹¹, H Sudderuddin¹¹, R Mackenzie¹¹, J George¹⁶; AOCS Group¹⁷; S Fereday¹⁸, J Hendley¹⁸, N Traficante¹⁸, H Steed¹⁹, J M Koziak²⁰, M Köbel²¹, I A McNeish²², T Goranova²³, D Ennis²², G Macintyre²³, D Silva De Silva²³, T Ramón Y Cajal²⁴, J García-Donas²⁵, S Hernando Polo²⁶, G C Rodriguez²⁷, K L Cushing-Haugen²⁸, H R Harris²⁹, C S Greene³⁰, R A Zelaya³¹, S Behrens³², R T Fortner³², P Sinn³³, E Herpel³⁴, J Lester³⁵, J Lubiński³⁶, O Oszurek³⁶, A Tołoczko³⁶, C Cybulski³⁶, J Menkiszak³⁷, C L Pearce³⁸, M C Pike³⁹, C Tseng⁴⁰, J Alsop⁴¹, V Rhenius⁴¹, H Song⁴¹, M Jimenez-Linan⁴², A M Piskorz²³, A Gentry-Maharaj⁴³, C Karpinskyj⁴³, M Widschwendter⁴⁴, N Singh⁴⁵, C J Kennedy⁴⁶, R Sharma⁴⁷, P R Harnett⁴⁸, B Gao⁴⁸, S E Johnatty⁴⁹, R Sayer⁵⁰, J Boros⁴⁶, S J Winham¹⁴, G L Keeney⁵¹, S H Kaufmann⁵², M C Larson¹⁴, H Luk⁵³, B Y Hernandez⁵³, P J Thompson⁵⁴, L R Wilkens⁵³, M E Carney⁵⁵, B Trabert⁵⁶, J Lissowska⁵⁷, L Brinton⁵⁶, M E Sherman⁵⁸, C Bodelon⁵⁶, S Hinsley⁵⁹, L A Lewsley⁵⁹, R Glasspool⁶⁰, S N Banerjee⁶¹, E A Stronach⁶², P Haluska⁶³, I Ray-Coquard⁶⁴, S Mahner⁶⁵, B Winterhoff⁶⁶, D Slamon⁶⁷, D A Levine⁶⁸, L E Kelemen⁶⁹, J Benitez⁷⁰, J Chang-Claude⁷¹, J Gronwald³⁶, A H Wu⁴⁰, U Menon⁴³, M T Goodman⁵⁴, J M Schildkraut⁷², N Wentzensen⁵⁶, R Brown⁷³, A Berchuck⁷⁴, G Chenevix-Trench⁴⁹, A deFazio⁴⁶, S A Gayther⁷⁵, M J García⁷⁶, M J Henderson⁷⁷, M A Rossing²⁹, A Beeghly-Fadiel⁷⁸, P A Fasching⁷⁹, S Orsulic³⁵, B Y Karlan³⁵, G E Konecny⁶⁷, D G Huntsman⁸⁰, D D Bowtell¹⁸, J D Brenton²³, J A Doherty⁸¹, P D P Pharoah⁸², S J Ramus⁸³

Collaborators, Affiliations

Collaborators

AOCS Group:
D Bowtell, G Chenevix-Trench, A Green, P Webb, A DeFazio, D Gertig, N Traficante, S Fereday, S Moore, J Hung, K Harrap, T Sadkowsky, N Pandeya, M Malt, A Mellon, R Robertson, T Vanden Bergh, M Jones, P Mackenzie, J Maidens, K Nattress, Y E Chiew, A Stenlake, H Sullivan, B Alexander, P Ashover, S Brown, T Corrish, L Green, L Jackman, K Ferguson, K Martin, A Martyn, B Ranieri, J White, V Jayde, P Mamers, L Bowes, L Galletta, D Giles, J Hendley, K Alsop, T Schmidt, H Shirley, C Ball, C Young, S Viduka, Hoa Tran, Sanela Bilic, Lydia Glavinas, Julia Brooks, R Stuart-Harris, F Kirsten, J Rutovitz, P Clingan, A Glasgow, A Proietto, S Braye, G Otton, J Shannon, T Bonaventura, J Stewart, S Begbie, M Friedlander, D Bell, S Baron-Hay, A Ferrier A, G Gard, D Nevell, N Pavlakis, S Valmadre, B Young, C Camaris, R Crouch, L Edwards, N Hacker, D Marsden, G Robertson, P Beale, J Beith, J Carter, C Dalrymple, R Houghton, P Russell, M Links, J Grygiel, J Hill, A Brand, K Byth, R Jaworski, P Harnett, R Sharma, G Wain, B Ward, D Papadimos, A Crandon, M Cummings, K Horwood, A Obermair, L Perrin, D Wyld, J Nicklin, M Davy, M K Oehler, C Hall, T Dodd, T Healy, K Pittman, D Henderson, J Miller, J Pierdes, P Blomfield, D Challis, R McIntosh, A Parker, B Brown, R Rome, D Allen, P Grant, S Hyde, R Laurie, M Robbie, D Healy, T Jobling, T Manolitsas, J McNealage, P Rogers, B Susil, E Sumithran, I Simpson, K Phillips, D Rischin, S Fox, D Johnson, S Lade, M Loughrey, N O'Callaghan, W Murray, P Waring, V Billson, J Pyman, D Neesham, M Quinn, C Underhill, R Bell, L F Ng, R Blum, V Ganju, I Hammond, Y Leung, A McCartney, M Buck, I Haviv, D Purdie, D Whiteman, N Zeps

Affiliations

¹ Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA.
² School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, Australia; CRUK Manchester Institute, The University of Manchester, Manchester, UK.
³ Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, USA.
⁴ British Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada.
⁵ British Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, Canada; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada.
⁶ School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, Australia.
⁷ Peter MacCallum Cancer Center, Melbourne, Australia.
⁸ Center for Cancer Prevention and Translational Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, USA.
⁹ Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA.
¹⁰ British Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
¹¹ British Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, Canada.
¹² Anatomical Pathology, Royal Women's Hospital, Parkville, Australia.
¹³ Department of Pathology, Duke University Hospital, Durham, USA.
¹⁴ Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, USA.
¹⁵ Department of Women's Health, Tuebingen University Hospital, Tuebingen, Germany.
¹⁶ The Jackson Laboratory for Genomic Medicine, Farmington, USA.
¹⁷ Peter MacCallum Cancer Center, Melbourne, Australia; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia.
¹⁸ Peter MacCallum Cancer Center, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.
¹⁹ Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Royal Alexandra Hospital, Edmonton, Canada.
²⁰ Alberta Health Services-Cancer Care, Calgary, Canada.
²¹ Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, Canada.
²² Division of Cancer and Ovarian Cancer Action Research Centre, Department Surgery & Cancer, Imperial College London, London, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
²³ Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
²⁴ Medical Oncology Service, Hospital Sant Pau, Barcelona, Spain.
²⁵ HM Hospitales D Centro Integral Oncológico HM Clara Campal, Madrid, Spain.
²⁶ Medical Oncology Service, Hospital Universitario Funcacion Alcorcon, Alcorcón, Spain.
²⁷ Division of Gynecologic Oncology, NorthShore University HealthSystem, University of Chicago, Evanston, USA.
²⁸ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA.
²⁹ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA; Department of Epidemiology, University of Washington, Seattle, USA.
³⁰ Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
³¹ Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, USA.
³² Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³³ Department of Pathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
³⁴ Department of Pathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany.
³⁵ David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, USA; Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, USA.
³⁶ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
³⁷ Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland.
³⁸ Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, USA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, USA.
³⁹ Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, USA; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, USA.
⁴⁰ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA.
⁴¹ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁴² Department of Pathology, Addenbrooke's Hospital NHS Trust, Cambridge, UK.
⁴³ MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, University College London, London, UK.
⁴⁴ Department of Women's Cancer, Institute for Women's Health, University College London, London, UK.
⁴⁵ Department of Pathology, Barts Health National Health Service Trust, London, UK.
⁴⁶ Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia; Department of Gynaecological Oncology, Westmead Hospital, Sydney, Australia.
⁴⁷ Pathology West ICPMR Westmead, Westmead Hospital, The University of Sydney, Sydney, Australia; University of Western Sydney at Westmead Hospital, Sydney, Australia.
⁴⁸ Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia; The Crown Princess Mary Cancer Centre Westmead, Sydney-West Cancer Network, Westmead Hospital, Sydney, Australia.
⁴⁹ Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁵⁰ Department of Gynaecological Oncology, Westmead Hospital, Sydney, Australia.
⁵¹ Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic, Rochester, USA.
⁵² Department of Oncology, Mayo Clinic, Rochester, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, USA.
⁵³ Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, USA.
⁵⁴ Samuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Cedars-Sinai Medical Center, Los Angeles, USA.
⁵⁵ John A. Burns School of Medicine, Department of Obstetrics and Gynecology, University of Hawaii, Honolulu, USA.
⁵⁶ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA.
⁵⁷ Department of Cancer Epidemiology and Prevention, M Sklodowska Curie National Research Institute of Oncology, Warsaw, Poland.
⁵⁸ Department of Health Sciences Research, Mayo Clinic College of Medicine, Jacksonville, USA.
⁵⁹ Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
⁶⁰ Department of Medical Oncology, Beatson West of Scotland Cancer Centre and University of Glasgow, Glasgow, UK.
⁶¹ The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK.
⁶² Division of Cancer and Ovarian Cancer Action Research Centre, Department Surgery & Cancer, Imperial College London, London, UK.
⁶³ Department of Oncology, Mayo Clinic, Rochester, USA.
⁶⁴ Centre Leon Berard and University Claude Bernard Lyon 1, Lyon, France.
⁶⁵ Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany.
⁶⁶ Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, USA.
⁶⁷ David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, USA.
⁶⁸ Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA; Gynecologic Oncology, Laura and Isaac Pearlmutter Cancer Center, NYU Langone Medical Center, New York, USA.
⁶⁹ Hollings Cancer Center and Department of Public Health Sciences, Medical University of South Carolina, Charleston, USA.
⁷⁰ Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain; Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
⁷¹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁷² Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, USA.
⁷³ Division of Cancer and Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London, UK.
⁷⁴ Department of Gynecologic Oncology, Duke University Hospital, Durham, USA.
⁷⁵ Center for Bioinformatics and Functional Genomics and the Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, USA.
⁷⁶ Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
⁷⁷ Children's Cancer Institute, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, Australia.
⁷⁸ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, USA.
⁷⁹ David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, USA; Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
⁸⁰ British Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada; Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, Canada.
⁸¹ Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, USA.
⁸² Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁸³ School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, Australia; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, Australia. Electronic address: s.ramus@unsw.edu.au.

PMID: 32473302
PMCID: PMC7484370
DOI: 10.1016/j.annonc.2020.05.019

Meta-Analysis

Prognostic gene expression signature for high-grade serous ovarian cancer

J Millstein et al. Ann Oncol. 2020 Sep.

. 2020 Sep;31(9):1240-1250.

doi: 10.1016/j.annonc.2020.05.019. Epub 2020 May 28.

Authors

Collaborators

AOCS Group:
D Bowtell, G Chenevix-Trench, A Green, P Webb, A DeFazio, D Gertig, N Traficante, S Fereday, S Moore, J Hung, K Harrap, T Sadkowsky, N Pandeya, M Malt, A Mellon, R Robertson, T Vanden Bergh, M Jones, P Mackenzie, J Maidens, K Nattress, Y E Chiew, A Stenlake, H Sullivan, B Alexander, P Ashover, S Brown, T Corrish, L Green, L Jackman, K Ferguson, K Martin, A Martyn, B Ranieri, J White, V Jayde, P Mamers, L Bowes, L Galletta, D Giles, J Hendley, K Alsop, T Schmidt, H Shirley, C Ball, C Young, S Viduka, Hoa Tran, Sanela Bilic, Lydia Glavinas, Julia Brooks, R Stuart-Harris, F Kirsten, J Rutovitz, P Clingan, A Glasgow, A Proietto, S Braye, G Otton, J Shannon, T Bonaventura, J Stewart, S Begbie, M Friedlander, D Bell, S Baron-Hay, A Ferrier A, G Gard, D Nevell, N Pavlakis, S Valmadre, B Young, C Camaris, R Crouch, L Edwards, N Hacker, D Marsden, G Robertson, P Beale, J Beith, J Carter, C Dalrymple, R Houghton, P Russell, M Links, J Grygiel, J Hill, A Brand, K Byth, R Jaworski, P Harnett, R Sharma, G Wain, B Ward, D Papadimos, A Crandon, M Cummings, K Horwood, A Obermair, L Perrin, D Wyld, J Nicklin, M Davy, M K Oehler, C Hall, T Dodd, T Healy, K Pittman, D Henderson, J Miller, J Pierdes, P Blomfield, D Challis, R McIntosh, A Parker, B Brown, R Rome, D Allen, P Grant, S Hyde, R Laurie, M Robbie, D Healy, T Jobling, T Manolitsas, J McNealage, P Rogers, B Susil, E Sumithran, I Simpson, K Phillips, D Rischin, S Fox, D Johnson, S Lade, M Loughrey, N O'Callaghan, W Murray, P Waring, V Billson, J Pyman, D Neesham, M Quinn, C Underhill, R Bell, L F Ng, R Blum, V Ganju, I Hammond, Y Leung, A McCartney, M Buck, I Haviv, D Purdie, D Whiteman, N Zeps

Affiliations

¹ Division of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA.
² School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, Australia; CRUK Manchester Institute, The University of Manchester, Manchester, UK.
³ Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, USA.
⁴ British Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada.
⁵ British Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, Canada; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada.
⁶ School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, Australia.
⁷ Peter MacCallum Cancer Center, Melbourne, Australia.
⁸ Center for Cancer Prevention and Translational Genomics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, USA.
⁹ Department of Pathology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, USA.
¹⁰ British Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
¹¹ British Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, Canada.
¹² Anatomical Pathology, Royal Women's Hospital, Parkville, Australia.
¹³ Department of Pathology, Duke University Hospital, Durham, USA.
¹⁴ Department of Health Science Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, USA.
¹⁵ Department of Women's Health, Tuebingen University Hospital, Tuebingen, Germany.
¹⁶ The Jackson Laboratory for Genomic Medicine, Farmington, USA.
¹⁷ Peter MacCallum Cancer Center, Melbourne, Australia; Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia.
¹⁸ Peter MacCallum Cancer Center, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.
¹⁹ Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Royal Alexandra Hospital, Edmonton, Canada.
²⁰ Alberta Health Services-Cancer Care, Calgary, Canada.
²¹ Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, Canada.
²² Division of Cancer and Ovarian Cancer Action Research Centre, Department Surgery & Cancer, Imperial College London, London, UK; Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
²³ Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
²⁴ Medical Oncology Service, Hospital Sant Pau, Barcelona, Spain.
²⁵ HM Hospitales D Centro Integral Oncológico HM Clara Campal, Madrid, Spain.
²⁶ Medical Oncology Service, Hospital Universitario Funcacion Alcorcon, Alcorcón, Spain.
²⁷ Division of Gynecologic Oncology, NorthShore University HealthSystem, University of Chicago, Evanston, USA.
²⁸ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA.
²⁹ Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, USA; Department of Epidemiology, University of Washington, Seattle, USA.
³⁰ Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
³¹ Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, USA.
³² Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
³³ Department of Pathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
³⁴ Department of Pathology, Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; National Center for Tumor Diseases, University Hospital and German Cancer Research Center, Heidelberg, Germany.
³⁵ David Geffen School of Medicine, Department of Obstetrics and Gynecology, University of California at Los Angeles, Los Angeles, USA; Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, USA.
³⁶ Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
³⁷ Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland.
³⁸ Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, USA; Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, USA.
³⁹ Department of Preventive Medicine, Keck School of Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, USA; Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, USA.
⁴⁰ Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA.
⁴¹ Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK.
⁴² Department of Pathology, Addenbrooke's Hospital NHS Trust, Cambridge, UK.
⁴³ MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, University College London, London, UK.
⁴⁴ Department of Women's Cancer, Institute for Women's Health, University College London, London, UK.
⁴⁵ Department of Pathology, Barts Health National Health Service Trust, London, UK.
⁴⁶ Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia; Department of Gynaecological Oncology, Westmead Hospital, Sydney, Australia.
⁴⁷ Pathology West ICPMR Westmead, Westmead Hospital, The University of Sydney, Sydney, Australia; University of Western Sydney at Westmead Hospital, Sydney, Australia.
⁴⁸ Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, Australia; The Crown Princess Mary Cancer Centre Westmead, Sydney-West Cancer Network, Westmead Hospital, Sydney, Australia.
⁴⁹ Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁵⁰ Department of Gynaecological Oncology, Westmead Hospital, Sydney, Australia.
⁵¹ Department of Laboratory Medicine and Pathology, Division of Anatomic Pathology, Mayo Clinic, Rochester, USA.
⁵² Department of Oncology, Mayo Clinic, Rochester, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, USA.
⁵³ Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, USA.
⁵⁴ Samuel Oschin Comprehensive Cancer Institute, Cancer Prevention and Genetics Program, Cedars-Sinai Medical Center, Los Angeles, USA.
⁵⁵ John A. Burns School of Medicine, Department of Obstetrics and Gynecology, University of Hawaii, Honolulu, USA.
⁵⁶ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, USA.
⁵⁷ Department of Cancer Epidemiology and Prevention, M Sklodowska Curie National Research Institute of Oncology, Warsaw, Poland.
⁵⁸ Department of Health Sciences Research, Mayo Clinic College of Medicine, Jacksonville, USA.
⁵⁹ Cancer Research UK Clinical Trials Unit, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.
⁶⁰ Department of Medical Oncology, Beatson West of Scotland Cancer Centre and University of Glasgow, Glasgow, UK.
⁶¹ The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, UK.
⁶² Division of Cancer and Ovarian Cancer Action Research Centre, Department Surgery & Cancer, Imperial College London, London, UK.
⁶³ Department of Oncology, Mayo Clinic, Rochester, USA.
⁶⁴ Centre Leon Berard and University Claude Bernard Lyon 1, Lyon, France.
⁶⁵ Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Munich, Germany.
⁶⁶ Department of Obstetrics, Gynecology and Women's Health, University of Minnesota, Minneapolis, USA.
⁶⁷ David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, USA.
⁶⁸ Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA; Gynecologic Oncology, Laura and Isaac Pearlmutter Cancer Center, NYU Langone Medical Center, New York, USA.
⁶⁹ Hollings Cancer Center and Department of Public Health Sciences, Medical University of South Carolina, Charleston, USA.
⁷⁰ Centro de Investigación en Red de Enfermedades Raras (CIBERER), Madrid, Spain; Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
⁷¹ Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Cancer Epidemiology Group, University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁷² Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, USA.
⁷³ Division of Cancer and Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London, UK.
⁷⁴ Department of Gynecologic Oncology, Duke University Hospital, Durham, USA.
⁷⁵ Center for Bioinformatics and Functional Genomics and the Cedars Sinai Genomics Core, Cedars-Sinai Medical Center, Los Angeles, USA.
⁷⁶ Human Cancer Genetics Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Biomedical Network on Rare Diseases (CIBERER), Madrid, Spain.
⁷⁷ Children's Cancer Institute, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, Australia.
⁷⁸ Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, USA.
⁷⁹ David Geffen School of Medicine, Department of Medicine Division of Hematology and Oncology, University of California at Los Angeles, Los Angeles, USA; Department of Gynecology and Obstetrics, Comprehensive Cancer Center ER-EMN, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
⁸⁰ British Columbia's Ovarian Cancer Research (OVCARE) Program, BC Cancer, Vancouver General Hospital, and University of British Columbia, Vancouver, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada; Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, Canada; Department of Molecular Oncology, BC Cancer Research Centre, Vancouver, Canada.
⁸¹ Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, USA.
⁸² Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, UK; Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
⁸³ School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, Australia; Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, Australia. Electronic address: s.ramus@unsw.edu.au.

PMID: 32473302
PMCID: PMC7484370
DOI: 10.1016/j.annonc.2020.05.019

Abstract

Background: 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.

Patients and methods: 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.

Results: 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.

Conclusion: 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.

Keywords: formalin-fixed paraffin-embedded; gene expression; high-grade serous ovarian cancer; overall survival; prognosis.

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Conflict of interest statement

Disclosure BYK served on Invitae Corporation's Advisory Board from 2017 to 2018. IAM has acted on the Advisory Boards for AstraZeneca, Clovis Oncology, Tesaro, Carrick Therapeutics and Takeda. His institution receives funding from AstraZeneca. RG is on the Advisory Boards for AstraZeneca, Tesaro, Clovis and Immunogen and does consultancy work for SOTIO. She has received support to attend conferences from AstraZeneca, Roche and Tesaro. Her institution has received research funding from Boehringer Ingelheim and Lilly/Ignyta and she is the national co-ordinating investigator for the UK for trials sponsored by AstraZeneca and Tesaro and site principal investigator for trials sponsored by AstraZeneca, Tesaro, Immunogen, Pfizer, Lilly and Clovis. PAF has received grants from Novartis, BioNtech and Cepheid as well as personal fees from Novartis, Roche, Pfizer, Celgene, Daiichi-Sankyo, TEVA, Astra Zeneca, Merck Sharp & Dohme, Myelo Therapeutics, MacroGenics, Eisai and Puma during the conduct of the study. JDB has acted on Advisory Boards for AstraZeneca and has received support from GSK to attend conferences. His institution receives funding from AstraZeneca and Aprea. UM has shares in Abcodia Ltd. Sandra Orsulic and Beth Y. Karlan have patents on predictive gene signatures in ovarian cancer (US010253368 and EU2908913). All remaining authors have declared no conflicts of interest.

Figures

**Figure 1.. Schematic of study design.**
*The TRI study was split across the training and validation sets due to 107 samples overlapping with the meta-analysis. GWAS, genome-wide association studies; HGSOC, high-grade serous ovarian cancer.

**Figure 2.. Receiver operator characteristic (ROC) curves for prognostic performance of the gene expression signature in independent high-grade serous ovarian cancer patients (testing data).**
There was no overlap between studies or patient data used to develop models (training data) and construct ROC curves and calculate area under the curve (AUC) values shown here (testing data). All models included age and stage as described in Methods section. TP denotes the true positive rate (sensitivity) and FP denotes the false positive rate (1 − specificity).

**Figure 3.. KaplaneMeier curves of overall survival for patients (A) in the training and (B) testing sets.**
Patients were assigned to quintiles (Q1–Q5) of the signature score including age and stage. Shaded areas indicate 95% confidence regions, only included for plots representing larger sample sizes. Because of limited sample size, the following plots represent all such patients in the entire dataset, training or testing: (C) no macroscopic residual disease after debulking surgery, (D) primary chemotherapy treatment ≥4 cycles of intravenous (IV) carboplatin area under the curve (AUC) 5 or 6 and paclitaxel 135 or 175 mg/m² every 3 weeks (actual dose known or presumed), (E) *BRCA1* or *BRCA2* germline mutation and (F) CD8 > 19.

See this image and copyright information in PMC

References

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Prognostic gene expression signature for high-grade serous ovarian cancer

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Prognostic gene expression signature for high-grade serous ovarian cancer

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