Prognostic gene expression signature for high-grade serous ovarian cancer

Millstein, J. et al. (2020) Prognostic gene expression signature for high-grade serous ovarian cancer. Annals of Oncology, 31(9), pp. 1240-1250. (doi: 10.1016/j.annonc.2020.05.019) (PMID:32473302) (PMCID:PMC7484370)

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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.

Item Type:Articles
Keywords:Formalin fixed paraffin embedded, gene expression, high grade serous ovarian cancer, overall survival, prognosis.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ennis, Dr Darren and Lewsley, Ms Liz-Anne and Hinsley, Miss Samantha and Mcneish, Professor Iain and Glasspool, Dr Rosalind
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., Fereday, S., Hendley, J., Traficante, N., Steed, H., Koziak, J. M., Köbel, M., Mcneish, I.A., Goranova, T., Ennis, D., Macintyre, G., Silva, D., Ramón Y Cajal, T., García-Donas, J., Polo, S. H., 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., 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., 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., and Ramus, S. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Annals of Oncology
Publisher:Elsevier
ISSN:0923-7534
ISSN (Online):1569-8041
Published Online:28 May 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Annals of Oncology 31(9): 1240-1250
Publisher Policy:Reproduced under a Creative Commons licence

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
169615Personalised biomarkers of response in high-grade serious ovarian cancerIain McNeishCancer Research UK (CRUK)C608/A15973CS - Clinical Research Garscube