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Prognostic gene expression signature for high-grade serous ovarian cancer

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Title: Prognostic gene expression signature for high-grade serous ovarian cancer
Authors: Millstein, J
Budden, T
Goode, EL
Anglesio, MS
Talhouk, A
Intermaggio, MP
Leong, HS
Chen, S
Elatre, W
Gilks, B
Nazeran, T
Hendley, J
Traficante, N
Steed, H
Koziak, JM
Köbel, M
McNeish, IA
Goranova, T
Ennis, D
Macintyre, G
Silva, D
Tołoczko, A
Ramón Y Cajal, T
García-Donas, J
Polo, SH
Rodriguez, GC
Cushing-Haugen, KL
Harris, HR
Greene, CS
Zelaya, RA
Behrens, S
Fortner, RT
Cybulski, C
Sinn, P
Herpel, E
Lester, J
Lubiński, J
Oszurek, O
Menkiszak, J
Pearce, CL
Pike, MC
Tseng, C
Alsop, J
Rhenius, V
Song, H
Jimenez-Linan, M
Larson, MC
Piskorz, A
Gentry-Maharaj, A
Karpinskyj, C
Widschwendter, M
Singh, N
Kennedy, CJ
Sharma, R
Harnett, PR
Gao, B
Johnatty, SE
Luk, H
Sayer, R
Boros, J
Winham, SJ
Keeney, GL
Kaufmann, SH
Hernandez, BY
Thompson, PJ
Wilkens, LR
Carney, ME
Trabert, B
Lissowska, J
Brinton, L
Sherman, ME
Gronwald, J
Bodelon, C
Hinsley, S
Lewsley, LA
Glasspool, R
Banerjee, SN
Stronach, EA
Haluska, P
Ray-Coquard, I
Mahner, S
Winterhoff, B
Wu, AH
Slamon, D
Levine, DA
Kelemen, LE
Benitez, J
Chang-Claude, J
Menon, U
Goodman, MT
Schildkraut, JM
Wentzensen, N
Brown, R
Berchuck, A
Chenevix-Trench, G
A deFazio
Volchek, M
Gayther, SA
García, MJ
Henderson, M
Rossing, MA
Beeghly-Fadiel, A
Fasching, PA
Orsulic, S
Karlan, BY
Konecny, GE
Huntsman, DG
Bentley, RC
Bowtell, DD
Brenton, JD
Doherty, JA
Pharoah, PDP
Ramus, SJ
Wang, C
Chiu, DS
Kommoss, S
Leung, SCY
Senz, J
Lum, A
Chow, V
Sudderuddin, H
Mackenzie, R
George, J
AOCS Group
Fereday, S
Item Type: Journal Article
Abstract: Background Median overall survival (OS) for women with high-grade serous ovarian cancer (HGSOC) is approximately four 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 overall survival in HGSOC patients. Patients and methods Expression of 513 genes, selected from a meta-analysis of 1455 tumours and other candidates, were measured using NanoString technology from formalin-fixed, paraffin-embedded (FFPE) tumour tissue from 3,769 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 fifteen 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 (FDR) < 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 (GES) conferred a greater than two-fold increase in risk of death [HR = 2.35 (2.02, 2.71); P < 0.001]. Median survival by GES quintile was 9.5 (8.3, --), 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.
Issue Date: 1-Sep-2020
Date of Acceptance: 7-May-2020
URI: http://hdl.handle.net/10044/1/80105
DOI: 10.1016/j.annonc.2020.05.019
ISSN: 0923-7534
Publisher: Oxford University Press (OUP)
Start Page: 1240
End Page: 1250
Journal / Book Title: Annals of Oncology
Volume: 31
Issue: 9
Copyright Statement: © 2020 The Authors. Published by Elsevier Ltd on behalf of European Society for Medical Oncology. This Journal Pre-print version is available open access under a CC-BY Licence (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
Cancer Research UK
Ovarian Cancer Action
Funder's Grant Number: RDB01
RG71079
n/a
Keywords: formalin-fixed paraffin-embedded
gene expression
high-grade serous ovarian cancer
overall survival
prognosis
AOCS Group
Oncology & Carcinogenesis
1112 Oncology and Carcinogenesis
Publication Status: Published
Online Publication Date: 2020-05-28
Appears in Collections:Department of Surgery and Cancer
Faculty of Medicine



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