The Ovarian Tumour Tissue Analysis Consortium: Stratified Prognosis of Ovarian Tumors (OTTA-SPOT) signature for high-grade serous ovarian cancer
Goode, E. L.
Anglesio, M. S.
Huntsman, D. G.
Bowtell, D. D.
Brenton, J. D.
Doherty, J. A.
Pharoah, P. P. D.
Ramus, S. J.
AffiliationDivision of Biostatistics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA.
MetadataShow full item record
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. Keywords: formalin-fixed paraffin-embedded; gene expression; high-grade serous ovarian cancer; overall survival; prognosis.
CitationMillstein J, Budden T, Goode EL, Anglesio MS, Talhouk A, Intermaggio MP, et al. Prognostic gene expression signature for high-grade serous ovarian cancer. Ann Oncol. 2020;26(13):20-1.
JournalClinical Cancer Research
- Cox-LASSO Analysis Reveals a Ten-lncRNA Signature to Predict Outcomes in Patients with High-Grade Serous Ovarian Cancer.
- Authors: Xu L, Wu Y, Che X, Zhao J, Wang F, Wang P, Qu X, Liu Y, Li Z
- Issue date: 2019 Dec
- HOXA4/HOXB3 gene expression signature as a biomarker of recurrence in patients with high-grade serous ovarian cancer following primary cytoreductive surgery and first-line adjuvant chemotherapy.
- Authors: Miller KR, Patel JN, Zhang Q, Norris EJ, Symanowski J, Michener C, Sehouli J, Braicu I, Destephanis DD, Sutker AP, Jones W, Livasy CA, Biscotti C, Ganapathi RN, Tait DL, Ganapathi MK
- Issue date: 2018 Apr
- A 2-Protein Signature Predicting Clinical Outcome in High-Grade Serous Ovarian Cancer.
- Authors: Jin C, Xue Y, Li Y, Bu H, Yu H, Zhang T, Zhang Z, Yan S, Lu N, Kong B
- Issue date: 2018 Jan
- Genomic Rearrangement Signatures and Clinical Outcomes in High-Grade Serous Ovarian Cancer.
- Authors: Hillman RT, Chisholm GB, Lu KH, Futreal PA
- Issue date: 2018 Mar 1
- The Impact of Stroma Admixture on Molecular Subtypes and Prognostic Gene Signatures in Serous Ovarian Cancer.
- Authors: Schwede M, Waldron L, Mok SC, Wei W, Basunia A, Merritt MA, Mitsiades CS, Parmigiani G, Harrington DP, Quackenbush J, Birrer MJ, Culhane AC
- Issue date: 2020 Feb