Prognostic gene expression signature for high-grade serous ovarian cancer

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 O...

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Autores: Millstein, Joshua, Budden, Timothy|||0000-0003-2500-2814, Goode, Ellen L.|||0000-0002-9094-8326, Anglesio, Michael|||0000-0003-1639-5003, Talhouk, Aline, Intermaggio, Maria Paola, Leong, Hueisan, Chen, Stephanie S., Elatre, Wafaa A., Gilks, Cyril Blake, Nazeran, Tayyebeh M., Volchek, Mila, Bentley, Rex C., Wang, Chen, Chiu, Derek S., Kommoss, Stefan, Leung, Samuel C. Y., Senz, Janine, Lum, Amy, Chow, Veronica, Sudderuddin, Hanwei|||0000-0002-1312-6492, Mackenzie, Robertson, George, Joshy, Fereday, Sian|||0000-0002-8559-8579, Hendley, Joy, Traficante, Nadia|||0000-0001-7459-8576, Steed, Helen|||0000-0002-0539-8906, Koziak, Jennifer M., Köbel, Martin|||0000-0002-6615-2037, McNeish, Iain A.|||0000-0002-9387-7586, Goranova, Teodora Evgenieva|||0000-0003-3848-2968, Ennis, Darren P., Macintyre, Geoff|||0000-0003-3906-467X, Silva De Silva, D., Ramon y Cajal, Teresa|||0000-0003-3490-3585, García Donas, J.|||0000-0001-7731-3601, Hernando-Polo, Susana, Rodriguez, Gustavo C., Cushing-Haugen, Kara L., Harris, Holly Ruth, Greene, Casey S.|||0000-0001-8713-9213, Zelaya, René A., Behrens, Sabine, Fortner, Renée T., Sinn, Hans-Peter|||0000-0003-2836-6699, Herpel, Esther, Lester, Jenny, Lubinski, Jan|||0000-0003-2931-3003, Oszurek, Oleg, Tołoczko, Aleksandra D., Cybulski, Cezary|||0000-0002-2819-3057, Menkiszak, Janusz Leszek, Pearce, Celeste Leigh, Pike, Malcolm C., Tseng, Chiuchen Cheng, Alsop, Jennifer, Rhenius, Valerie, Song, Hongan, Jimenez-Liñan, Mercedes, Piskorz, Anna M., Gentry-Maharaj, Aleksandra, Karpinskyj, Chloe, Widschwendter, M., Singh, Naveena K., Kennedy, Catherine J.|||0000-0002-4465-5784, Harnett, Paul R., Gao, Bo, Johnatty, Sharon E., Sayer, Robyn A., Boros, Jessica, Winham, Stacey J.|||0000-0002-8492-9102, Keeney, Gary L., Kaufmann, Scott H., Larson, Melissa C., Luk, Hugh W., Hernandez, Brenda Y., Thompson, Pamela J., Wilkens, Lynne Ross, Carney, Michael E., Trabert, Britton|||0000-0002-1539-6090, Lissowska, Jolanta, Brinton, Louise Annette, Sherman, Mark E., Bodelón, Clara, Hinsley, Samantha, Lewsley, Liz Anne, Glasspool, Rosalind M., Banerjee, Susana|||0000-0002-8840-7934, Stronach, Euan A., Haluska, Paul J., Ray-Coquard, Isabelle Laure, Mahner, Sven, Winterhoff, Boris J. N., Slamon, Dennis J., Levine, Douglas A.|||0000-0003-1038-8232, Kelemen, Linda E., Benitez, Javier J., Chang-Claude, J., Gronwald, Jacek, Wu, Anna H., Menon, Usha|||0000-0003-3708-1732, Goodman, Marc T., Schildkraut, Joellen M., Wentzensen, Nicolas A., Brown, Robert, Berchuck, Andrew, Gayther, Simon A.|||0000-0001-7937-5443, García, M. J., Henderson, Michelle J., Rossing, Mary Anne, Beeghly-Fadiel, Alicia|||0000-0001-9913-732X, Fasching, Peter Andreas, Orsulic, Sandra|||0000-0001-5119-8721, Karlan, Beth Y.|||0000-0002-9451-2933, Konecny, Gottfried Ewald, Huntsman, David G.|||0000-0003-4934-3322, Brenton, James D.|||0000-0002-5738-6683, Doherty, Jennifer Anne, Pharoah, Paul D. P.|||0000-0001-8494-732X, Ramus, Susan J.|||0000-0003-0005-7798
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:284138
Acceso en línea:https://ddd.uab.cat/record/284138
https://dx.doi.org/urn:doi:10.1016/j.annonc.2020.05.019
Access Level:acceso abierto
Palabra clave:Formalin-fixed paraffin-embedded
Gene expression
High-grade serous ovarian cancer
Overall survival
Prognosis
Descripción
Sumario: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. 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. 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. 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.

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