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dc.contributor.authorMillstein, J
dc.contributor.authorBudden, T
dc.contributor.authorGoode, EL
dc.contributor.authorAnglesio, MS
dc.contributor.authorTalhouk, A
dc.contributor.authorIntermaggio, MP
dc.contributor.authorLeong, HS
dc.contributor.authorChen, S
dc.contributor.authorElatre, W
dc.contributor.authorGilks, B
dc.contributor.authorNazeran, T
dc.contributor.authorVolchek, M
dc.contributor.authorBentley, RC
dc.contributor.authorWang, C
dc.contributor.authorChiu, DS
dc.contributor.authorKommoss, S
dc.contributor.authorLeung, SCY
dc.contributor.authorSenz, J
dc.contributor.authorLum, A
dc.contributor.authorChow, V
dc.contributor.authorSudderuddin, H
dc.contributor.authorMackenzie, R
dc.contributor.authorGeorge, J
dc.contributor.authorAOCS Group
dc.contributor.authorFereday, S
dc.contributor.authorHendley, J
dc.contributor.authorTraficante, N
dc.contributor.authorSteed, H
dc.contributor.authorKoziak, JM
dc.contributor.authorKöbel, M
dc.contributor.authorMcNeish, IA
dc.contributor.authorGoranova, T
dc.contributor.authorEnnis, D
dc.contributor.authorMacintyre, G
dc.contributor.authorSilva De Silva, D
dc.contributor.authorRamón Y Cajal, T
dc.contributor.authorGarcía-Donas, J
dc.contributor.authorHernando Polo, S
dc.contributor.authorRodriguez, GC
dc.contributor.authorCushing-Haugen, KL
dc.contributor.authorHarris, HR
dc.contributor.authorGreene, CS
dc.contributor.authorZelaya, RA
dc.contributor.authorBehrens, S
dc.contributor.authorFortner, RT
dc.contributor.authorSinn, P
dc.contributor.authorHerpel, E
dc.contributor.authorLester, J
dc.contributor.authorLubiński, J
dc.contributor.authorOszurek, O
dc.contributor.authorTołoczko, A
dc.contributor.authorCybulski, C
dc.contributor.authorMenkiszak, J
dc.contributor.authorPearce, CL
dc.contributor.authorPike, MC
dc.contributor.authorTseng, C
dc.contributor.authorAlsop, J
dc.contributor.authorRhenius, V
dc.contributor.authorSong, H
dc.contributor.authorJimenez-Linan, M
dc.contributor.authorPiskorz, AM
dc.contributor.authorGentry-Maharaj, A
dc.contributor.authorKarpinskyj, C
dc.contributor.authorWidschwendter, M
dc.contributor.authorSingh, N
dc.contributor.authorKennedy, CJ
dc.contributor.authorSharma, R
dc.contributor.authorHarnett, PR
dc.contributor.authorGao, B
dc.contributor.authorJohnatty, SE
dc.contributor.authorSayer, R
dc.contributor.authorBoros, J
dc.contributor.authorWinham, SJ
dc.contributor.authorKeeney, GL
dc.contributor.authorKaufmann, SH
dc.contributor.authorLarson, MC
dc.contributor.authorLuk, H
dc.contributor.authorHernandez, BY
dc.contributor.authorThompson, PJ
dc.contributor.authorWilkens, LR
dc.contributor.authorCarney, ME
dc.contributor.authorTrabert, B
dc.contributor.authorLissowska, J
dc.contributor.authorBrinton, L
dc.contributor.authorSherman, ME
dc.contributor.authorBodelon, C
dc.contributor.authorHinsley, S
dc.contributor.authorLewsley, LA
dc.contributor.authorGlasspool, R
dc.contributor.authorBanerjee, SN
dc.contributor.authorStronach, EA
dc.contributor.authorHaluska, P
dc.contributor.authorRay-Coquard, I
dc.contributor.authorMahner, S
dc.contributor.authorWinterhoff, B
dc.contributor.authorSlamon, D
dc.contributor.authorLevine, DA
dc.contributor.authorKelemen, LE
dc.contributor.authorBenitez, J
dc.contributor.authorChang-Claude, J
dc.contributor.authorGronwald, J
dc.contributor.authorWu, AH
dc.contributor.authorMenon, U
dc.contributor.authorGoodman, MT
dc.contributor.authorSchildkraut, JM
dc.contributor.authorWentzensen, N
dc.contributor.authorBrown, R
dc.contributor.authorBerchuck, A
dc.contributor.authorChenevix-Trench, G
dc.contributor.authordeFazio, A
dc.contributor.authorGayther, SA
dc.contributor.authorGarcía, MJ
dc.contributor.authorHenderson, MJ
dc.contributor.authorRossing, MA
dc.contributor.authorBeeghly-Fadiel, A
dc.contributor.authorFasching, PA
dc.contributor.authorOrsulic, S
dc.contributor.authorKarlan, BY
dc.contributor.authorKonecny, GE
dc.contributor.authorHuntsman, DG
dc.contributor.authorBowtell, DD
dc.contributor.authorBrenton, JD
dc.contributor.authorDoherty, JA
dc.contributor.authorPharoah, PDP
dc.contributor.authorRamus, SJ
dc.date.accessioned2020-07-08T10:24:43Z
dc.date.issued2020-09
dc.identifier.citationAnnals of oncology : official journal of the European Society for Medical Oncology, 2020, 31 (9), pp. 1240 - 1250
dc.identifier.issn0923-7534
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3824
dc.identifier.eissn1569-8041
dc.identifier.doi10.1016/j.annonc.2020.05.019
dc.description.abstractBackground 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.
dc.formatPrint-Electronic
dc.format.extent1240 - 1250
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectAOCS Group
dc.subjectHumans
dc.subjectCystadenocarcinoma, Serous
dc.subjectOvarian Neoplasms
dc.subjectPrognosis
dc.subjectProportional Hazards Models
dc.subjectSurvival Analysis
dc.subjectFemale
dc.subjectTranscriptome
dc.titlePrognostic gene expression signature for high-grade serous ovarian cancer.
dc.typeJournal Article
dcterms.dateAccepted2020-05-06
rioxxterms.versionofrecord10.1016/j.annonc.2020.05.019
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2020-09
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfAnnals of oncology : official journal of the European Society for Medical Oncology
pubs.issue9
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Medicine (Brown Epigenetic Therapy)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Medicine (Brown Epigenetic Therapy)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume31
pubs.embargo.termsNot known
icr.researchteamMedicine (Brown Epigenetic Therapy)en_US
dc.contributor.icrauthorBrown, Roberten
dc.contributor.icrauthorBanerjee, Susanaen


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