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@article{Millstein:2020:10.1016/j.annonc.2020.05.019,
author = {Millstein, J and Budden, T and Goode, EL and Anglesio, MS and Talhouk, A and Intermaggio, MP and Leong, HS and Chen, S and Elatre, W and Gilks, B and Nazeran, T and Volchek, M and Bentley, RC and Wang, C and Chiu, DS and Kommoss, S and Leung, SCY and Senz, J and Lum, A and Chow, V and Sudderuddin, H and Mackenzie, R and George, J and AOCS, Group and Fereday, S and Hendley, J and Traficante, N and Steed, H and Koziak, JM and Köbel, M and McNeish, IA and Goranova, T and Ennis, D and Macintyre, G and Silva, D and Ramón, Y Cajal T and García-Donas, J and Polo, SH and Rodriguez, GC and Cushing-Haugen, KL and Harris, HR and Greene, CS and Zelaya, RA and Behrens, S and Fortner, RT and Sinn, P and Herpel, E and Lester, J and Lubiski, J and Oszurek, O and Tooczko, A and Cybulski, C and Menkiszak, J and Pearce, CL and Pike, MC and Tseng, C and Alsop, J and Rhenius, V and Song, H and Jimenez-Linan, M and Piskorz, A and Gentry-Maharaj, A and Karpinskyj, C and Widschwendter, M and Singh, N and Kenn},
doi = {10.1016/j.annonc.2020.05.019},
journal = {Annals of Oncology},
pages = {1240--1250},
title = {Prognostic gene expression signature for high-grade serous ovarian cancer},
url = {http://dx.doi.org/10.1016/j.annonc.2020.05.019},
volume = {31},
year = {2020}
}

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TY  - JOUR
AB  - BackgroundMedian 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 methodsExpression 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.ResultsExpression 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.ConclusionThe 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.
AU  - Millstein,J
AU  - Budden,T
AU  - Goode,EL
AU  - Anglesio,MS
AU  - Talhouk,A
AU  - Intermaggio,MP
AU  - Leong,HS
AU  - Chen,S
AU  - Elatre,W
AU  - Gilks,B
AU  - Nazeran,T
AU  - Volchek,M
AU  - Bentley,RC
AU  - Wang,C
AU  - Chiu,DS
AU  - Kommoss,S
AU  - Leung,SCY
AU  - Senz,J
AU  - Lum,A
AU  - Chow,V
AU  - Sudderuddin,H
AU  - Mackenzie,R
AU  - George,J
AU  - AOCS,Group
AU  - Fereday,S
AU  - Hendley,J
AU  - Traficante,N
AU  - Steed,H
AU  - Koziak,JM
AU  - Köbel,M
AU  - McNeish,IA
AU  - Goranova,T
AU  - Ennis,D
AU  - Macintyre,G
AU  - Silva,D
AU  - Ramón,Y Cajal T
AU  - García-Donas,J
AU  - Polo,SH
AU  - Rodriguez,GC
AU  - Cushing-Haugen,KL
AU  - Harris,HR
AU  - Greene,CS
AU  - Zelaya,RA
AU  - Behrens,S
AU  - Fortner,RT
AU  - Sinn,P
AU  - Herpel,E
AU  - Lester,J
AU  - Lubiski,J
AU  - Oszurek,O
AU  - Tooczko,A
AU  - Cybulski,C
AU  - Menkiszak,J
AU  - Pearce,CL
AU  - Pike,MC
AU  - Tseng,C
AU  - Alsop,J
AU  - Rhenius,V
AU  - Song,H
AU  - Jimenez-Linan,M
AU  - Piskorz,A
AU  - Gentry-Maharaj,A
AU  - Karpinskyj,C
AU  - Widschwendter,M
AU  - Singh,N
AU  - Kennedy,CJ
AU  - Sharma,R
AU  - Harnett,PR
AU  - Gao,B
AU  - Johnatty,SE
AU  - Sayer,R
AU  - Boros,J
AU  - Winham,SJ
AU  - Keeney,GL
AU  - Kaufmann,SH
AU  - Larson,MC
AU  - Luk,H
AU  - Hernandez,BY
AU  - Thompson,PJ
AU  - Wilkens,LR
AU  - Carney,ME
AU  - Trabert,B
AU  - Lissowska,J
AU  - Brinton,L
AU  - Sherman,ME
AU  - Bodelon,C
AU  - Hinsley,S
AU  - Lewsley,LA
AU  - Glasspool,R
AU  - Banerjee,SN
AU  - Stronach,EA
AU  - Haluska,P
AU  - Ray-Coquard,I
AU  - Mahner,S
AU  - Winterhoff,B
AU  - Slamon,D
AU  - Levine,DA
AU  - Kelemen,LE
AU  - Benitez,J
AU  - Chang-Claude,J
AU  - Gronwald,J
AU  - Wu,AH
AU  - Menon,U
AU  - Goodman,MT
AU  - Schildkraut,JM
AU  - Wentzensen,N
AU  - Brown,R
AU  - Berchuck,A
AU  - Chenevix-Trench,G
AU  - A,deFazio
AU  - Gayther,SA
AU  - García,MJ
AU  - Henderson,M
AU  - Rossing,MA
AU  - Beeghly-Fadiel,A
AU  - Fasching,PA
AU  - Orsulic,S
AU  - Karlan,BY
AU  - Konecny,GE
AU  - Huntsman,DG
AU  - Bowtell,DD
AU  - Brenton,JD
AU  - Doherty,JA
AU  - Pharoah,PDP
AU  - Ramus,SJ
DO  - 10.1016/j.annonc.2020.05.019
EP  - 1250
PY  - 2020///
SN  - 0923-7534
SP  - 1240
TI  - Prognostic gene expression signature for high-grade serous ovarian cancer
T2  - Annals of Oncology
UR  - http://dx.doi.org/10.1016/j.annonc.2020.05.019
UR  - http://hdl.handle.net/10044/1/80105
VL  - 31
ER  -

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