| 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; Volchek, M; Bentley, RC; Wang, C; Chiu, DS; Kommoss, S; Leung, SCY; Senz, J; Lum, A; Chow, V; Sudderuddin, H; Mackenzie, R; George, J; Bowtell, DD; Chenevix-Trench, G; Green, A; Webb, P; deFazio, A; Gertig, D; Traficante, N; Fereday, S; Moore, S; Hung, J; Harrap, K; Sadkowsky, T; Pandeya, N; Malt, M; Mellon, A; Robertson, R; Vanden Bergh, T; Jones, M; Mackenzie, P; Maidens, J; Nattress, K; Chiew, YE; Stenlake, A; Sullivan, H; Alexander, B; Ashover, P; Brown, S; Corrish, T; Green, L; Jackman, L; Ferguson, K; Martin, K; Martyn, A; Ranieri, B; White, J; Jayde, V; Mamers, P; Bowes, L; Galletta, L; Giles, D; Hendley, J; Alsop, K; Schmidt, T; Shirley, H; Ball, C; Young, C; Viduka, S; Tran, H; Bilic, S; Glavinas, L; Brooks, J; Stuart-Harris, R; Kirsten, F; Rutovitz, J; Clingan, P; Glasgow, A; Proietto, A; Braye, S; Otton, G; Shannon, J; Bonaventura, T; Stewart, J; Begbie, S; Friedlander, M; Bell, D; Baron-Hay, S; Ferrier,a, A; Gard, G; Nevell, D; Pavlakis, N; Valmadre, S; Young, B; Camaris, C; Crouch, R; Edwards, L; Hacker, N; Marsden, D |
| Publisher Information: |
ELSEVIER |
| Publication Year: |
2020 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
BACKGROUND: 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0923-7534 |
| Relation: |
NHMRC/310670; NHMRC/400281; NHMRC/628903; NHMRC/400413; https://hdl.handle.net/11343/247694 |
| Availability: |
https://hdl.handle.net/11343/247694 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0 ; CC BY-NC-ND |
| Accession Number: |
edsbas.D4159AD2 |
| Database: |
BASE |