Prognostic gene expression signature for high-grade serous ovarian cancer Journal Article
| Authors: | Millstein, J.; Budden, T.; Goode, E. L.; Anglesio, M. S.; Talhouk, A.; Intermaggio, M. P.; Leong, H. S.; Chen, S.; Elatre, W.; Gilks, B.; Nazeran, T.; Volchek, M.; Bentley, R. C.; Wang, C.; Chiu, D. S.; Kommoss, S.; Leung, S. C. Y.; Senz, J.; Lum, A.; Chow, V.; Sudderuddin, H.; Mackenzie, R.; George, J.; AOCS Group; Fereday, S.; Hendley, J.; Traficante, N.; Steed, H.; Koziak, J. M.; Köbel, M.; McNeish, I. A.; Goranova, T.; Ennis, D.; Macintyre, G.; Silva De Silva, D.; Ramón y Cajal, T.; García-Donas, J.; Hernando Polo, S.; Rodriguez, G. C.; Cushing-Haugen, K. L.; Harris, H. R.; Greene, C. S.; Zelaya, R. A.; Behrens, S.; Fortner, R. T.; Sinn, P.; Herpel, E.; Lester, J.; Lubiński, J.; Oszurek, O.; Tołoczko, A.; Cybulski, C.; Menkiszak, J.; Pearce, C. L.; Pike, M. C.; Tseng, C.; Alsop, J.; Rhenius, V.; Song, H.; Jimenez-Linan, M.; Piskorz, A. M.; Gentry-Maharaj, A.; Karpinskyj, C.; Widschwendter, M.; Singh, N.; Kennedy, C. J.; Sharma, R.; Harnett, P. R.; Gao, B.; Johnatty, S. E.; Sayer, R.; Boros, J.; Winham, S. J.; Keeney, G. L.; Kaufmann, S. H.; Larson, M. C.; Luk, H.; Hernandez, B. Y.; Thompson, P. J.; Wilkens, L. R.; Carney, M. E.; Trabert, B.; Lissowska, J.; Brinton, L.; Sherman, M. E.; Bodelon, C.; Hinsley, S.; Lewsley, L. A.; Glasspool, R.; Banerjee, S. N.; Stronach, E. A.; Haluska, P.; Ray-Coquard, I.; Mahner, S.; Winterhoff, B.; Slamon, D.; Levine, D. A.; Kelemen, L. E.; Benitez, J.; Chang-Claude, J.; Gronwald, J.; Wu, A. H.; Menon, U.; Goodman, M. T.; Schildkraut, J. M.; Wentzensen, N.; Brown, R.; Berchuck, A.; Chenevix-Trench, G.; deFazio, A.; Gayther, S. A.; García, M. J.; Henderson, M. J.; Rossing, M. A.; Beeghly-Fadiel, A.; Fasching, P. A.; Orsulic, S.; Karlan, B. Y.; Konecny, G. E.; Huntsman, D. G.; Bowtell, D. D.; Brenton, J. D.; Doherty, J. A.; Pharoah, P. D. P.; Ramus, S. J. |
| Article Title: | Prognostic gene expression signature for high-grade serous ovarian cancer |
| Abstract: | 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. © 2020 The Authors |
| Keywords: | overall survival; gene expression; prognosis; formalin-fixed paraffin-embedded; high-grade serous ovarian cancer |
| Journal Title: | Annals of Oncology |
| Volume: | 31 |
| Issue: | 9 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2020-09-01 |
| Start Page: | 1240 |
| End Page: | 1250 |
| Language: | English |
| DOI: | 10.1016/j.annonc.2020.05.019 |
| PROVIDER: | scopus |
| PUBMED: | 32473302 |
| PMCID: | PMC7484370 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 September 2020 -- Source: Scopus |
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