Prognostic gene expression signature for high-grade serous ovarian cancer

Millstein J, Budden T, Goode EL, Anglesio MS, Talhouk A, Intermaggio MP, Leong HS, Chen S, Elatre W, Gilks B, Nazeran T, Volchek M, Bentley RC, Wang C, Chiu DS, Kommoss S, Leung SC, Senz J, Lum A, Chow V, Sudderuddin H, Mackenzie R, George J, Fereday S, Hendley J, Traficante N, Steed H, Koziak JM, Köbel M, McNeish IA, Goranova T, Ennis D, Macintyre G, Silva De Silva D, Ramón y Cajal T, García-Donas J, Hernando Polo S, Rodriguez GC, Cushing-Haugen KL, Harris HR, Greene CS, Zelaya RA, Behrens S, Fortner RT, Sinn P, Herpel E, Lester J, Lubiński J, Oszurek O, Tołoczko A, Cybulski C, Menkiszak J, Pearce CL, Pike MC, Tseng C, Alsop J, Rhenius V, Song H, Jimenez-Linan M, Piskorz AM, Gentry-Maharaj A, Karpinskyj C, Widschwendter M, Singh N, Kennedy CJ, Sharma R, Harnett PR, Gao B, Johnatty SE, Sayer R, Boros J, Winham SJ, Keeney GL, Kaufmann SH, Larson MC, Luk H, Hernandez BY, Thompson PJ, Wilkens LR, Carney ME, Trabert B, Lissowska J, Brinton L, Sherman ME, Bodelon C, Hinsley S, Lewsley LA, Glasspool R, Banerjee SN, Stronach EA, Haluska P, Ray-Coquard I, Mahner S, Winterhoff B, Slamon D, Levine DA, Kelemen LE, Benitez J, Chang-Claude J, Gronwald J, Wu AH, Menon U, Goodman MT, Schildkraut JM, Wentzensen N, Brown R, Berchuck A, Chenevix-Trench G, deFazio A, Gayther SA, García MJ, Henderson MJ, Rossing MA, Beeghly-Fadiel A, Fasching P, Orsulic S, Karlan BY, Konecny GE, Huntsman DG, Bowtell DD, Brenton JD, Doherty JA, Pharoah PD, Ramus SJ (2020)

Publication Type: Journal article

Publication year: 2020

Journal

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.

Authors with CRIS profile

Involved external institutions

QIMR Berghofer Medical Research Institute (früher: the Queensland Institute of Medical Research) Australia (AU) Keck School of Medicine of USC United States (USA) (US) University of New South Wales (UNSW) Australia (AU) Peter MacCallum Cancer Centre Australia (AU) University of British Columbia Canada (CA) Mayo Clinic United States (USA) (US) Duke University Health System United States (USA) (US) Jackson Laboratory for Genomic Medicine United States (USA) (US) Royal Alexandra Hospital (RAH) Canada (CA) Imperial College London / The Imperial College of Science, Technology and Medicine United Kingdom (GB) Geisel School of Medicine United States (USA) (US) University of Calgary Canada (CA) Fred Hutchinson Cancer Research Center United States (USA) (US) University of Cambridge United Kingdom (GB) Alberta Health Services (AHS) Canada (CA) NorthShore University HealthSystem United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Universitätsklinikum Heidelberg Germany (DE) University of California Los Angeles (UCLA) United States (USA) (US) Pomeranian Medical University / Pomorski Uniwersytet Medyczny w Szczecinie (PMU) Poland (PL) University College London (UCL) United Kingdom (GB) University of Michigan–Ann Arbor United States (USA) (US) University of Sydney (USYD) Australia (AU) University of Hawaiʻi at Mānoa United States (USA) (US) National Cancer Institute (NCI) United States (USA) (US) Maria Skłodowska-Curie Institute of Oncology / Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie Poland (PL) Cedars-Sinai Medical Center United States (USA) (US) University of Hawaii (U.H.) United States (USA) (US) Westmead Hospital Australia (AU) Memorial Sloan Kettering Cancer Center United States (USA) (US) Medical University of South Carolina (MUSC) United States (USA) (US) Klinikum der Universität München Germany (DE) Ciber de Enfermedades Raras (CIBERER) Spain (ES) Royal Marsden Hospital / The Royal Marsden NHS Foundation Trust United Kingdom (GB) Beatson West of Scotland Cancer Centre (BWSCC) United Kingdom (GB) Université Claude Bernard Lyon 1 (UCB) France (FR) University of Minnesota (UMN) United States (USA) (US) Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) Spain (ES) Vanderbilt University Medical Center United States (USA) (US) Huntsman Cancer Institute United States (USA) (US) University of Glasgow United Kingdom (GB) Addenbrooke's Hospital United Kingdom (GB) Barts Health NHS Trust United Kingdom (GB) The Royal Women's Hospital Australia (AU) Perelman School of Medicine University of Pennsylvania United States (USA) (US) Hospital Universitario Fundación Alcorcón (HUFA) Spain (ES) Hospital Clínic de Barcelona Spain (ES) Universitätsklinikum Tübingen Germany (DE) HM Hospitales Spain (ES) Emory University United States (USA) (US)

How to cite

APA:

Millstein, J., Budden, T., Goode, E.L., Anglesio, M.S., Talhouk, A., Intermaggio, M.P.,... Ramus, S.J. (2020). Prognostic gene expression signature for high-grade serous ovarian cancer. Annals of Oncology. https://doi.org/10.1016/j.annonc.2020.05.019

MLA:

Millstein, J., et al. "Prognostic gene expression signature for high-grade serous ovarian cancer." Annals of Oncology (2020).

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