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Prognostically relevant gene signatures of high-grade serous ovarian carcinoma

Journal of Clinical Investigation. Volume 123, Issue 1, 2 January 2013 10.1172/JCI65833

Because of the high risk of recurrence in high-grade serous ovarian carcinoma (HGS-OvCa), the development of outcome predictors could be valuable for patient stratification. Using the catalog of The Cancer Genome Atlas (TCGA), we developed subtype and survival gene expression signatures, which, when combined, provide a prognostic model of HGS-OvCa classification, named “Classification of Ovarian Cancer” (CLOVAR). We validated CLOVAR on an independent dataset consisting of 879 HGS-OvCa expression profiles. The worst outcome group, accounting for 23% of all cases, was associated with a median survival of 23 months and a platinum resistance rate of 63%, versus a median survival of 46 months and platinum resistance rate of 23% in other cases. Associating the outcome prediction model with BRCA1/BRCA2 mutation status, residual disease after surgery, and disease stage further optimized outcome classification. Ovarian cancer is a disease in urgent need of more effective therapies. The spectrum of outcomes observed here and their association with CLOVAR signatures suggests variations in underlying tumor biology. Prospective validation of the CLOVAR model in the context of additional prognostic variables may provide a rationale for optimal combination of patient and treatment regimens.

Data in the GDC

Training Data Set

    • All supplementary materials listed below in one zip archive.
    • Unified gene expression profiles of 489 ovarian cancers, as published by The Cancer Genome Atlas Research Network, Nature, 2011 (PMID 21720365) and further discussed in Verhaak et al, JCI, 2013 (PMID 23257362). Data is based on integrating gene expression from Affymetrix U133A, Agilent and Affymetrix HuEx platforms, as discussed in Wang et al, PLOS One, 2011 (PMID 21436879). TCGA_489_UE.gct
    • All samples with a positive silhouette value after NMF clustering. TCGA_489_UE.k4.posSilhouette.txt
    • Gene expression profile based NMF clustering of 489 ovarian cancers as published by The Cancer Genome Atlas Research Network, Nature, 2011 (PMID 21720365). TCGA_489_UE.k4.txt
    • Gene expression matrix of 489 ovarian cancers versus the top 1,500 most variable expressed genes (as estimated by the maximum absolute deviation), used for input to non-negative matrix factorization (NMF) clustering. TCGA_489_UE.top1500.txt

Validation Data Set

    • Gene-centric expression profiles from 169 ovarian cancers, published by Bonome et al, Cancer Res, 2008 (PMID 18593951). Bonome_169.gct
    • Gene-centric expression profiles from 157 ovarian cancers, published by Crijns et al, PLOS Medicine, 2009 (PMID 19192944). Crijns_157.collapsed.gct
    • Gene-centric expression profiles from 68 ovarian cancers, published by Denkert et al, J Pathol, 2009 (PMID 19294737). Denkert_68.gct
    • Gene-centric expression profiles from 119 ovarian cancers, published by Dressman et al, JCO , 2007 (PMID 17290060). Dressman_119.gct
    • Gene-centric Affymetrix U133A expression profiles from 64 ovarian cancers not included in the original TCGA publication (Nature, 2011). TCGA_extra_64.gct
    • Gene-centric expression profiles from Tothill et al, Clin Cancer Res, 2008 (PMID 18698038). Tothill_245.gct
    • Gene-centric expression profiles from Yoshihara et al, PLOS One, 2010 (PMID 20300634). Yoshihara_110.collapsed.gct

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