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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, Valerie
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, James
dc.contributor.authorDoherty, JA
dc.contributor.authorPharoah, Paul
dc.contributor.authorRamus, SJ
dc.date.accessioned2020-06-04T23:30:26Z
dc.date.available2020-06-04T23:30:26Z
dc.date.issued2020-09
dc.identifier.issn0923-7534
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/306124
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.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAll rights reserved
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.typeArticle
prism.endingPage1250
prism.issueIdentifier9
prism.publicationDate2020
prism.publicationNameAnn Oncol
prism.startingPage1240
prism.volume31
dc.identifier.doi10.17863/CAM.53203
dcterms.dateAccepted2020-05-06
rioxxterms.versionofrecord10.1016/j.annonc.2020.05.019
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2020-09
dc.contributor.orcidRhenius, Valerie [0000-0003-4215-3235]
dc.contributor.orcidBrenton, James [0000-0002-5738-6683]
dc.contributor.orcidPharoah, Paul [0000-0001-8494-732X]
dc.identifier.eissn1569-8041
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research UK (CRUK-A15973)
pubs.funder-project-idCancer Research UK (CRUK-A15601)
cam.orpheus.successMon Jun 08 08:22:11 BST 2020 - Embargo updated
rioxxterms.freetoread.startdate2021-05-27


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