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KONECNY, Gottfried E; CHEN WANG; GOSTOUT, Bobbie; PODRATZ, Karl C; KEENEY, Gary; WANG, He-Jing; HARTMANN, Lynn C; SLAMON, Dennis J; GOODE, Ellen L; HAMIDI, Habib; WINTERHOFF, Boris; KALLI, Kimberly R; DERING, Judy; GINTHER, Charles; CHEN, Hsiao-Wang; DOWDY, Sean; CLIBY, William
JNCI : Journal of the National Cancer Institute, 10/2014, Volume: 106, Issue: 10Journal Article
Molecular classification of high-grade serous ovarian cancer (HGSOC) using transcriptional profiling has proven to be complex and difficult to validate across studies. We determined gene expression profiles of 174 well-annotated HGSOCs and demonstrate prognostic significance of the prespecified TCGA Network gene signatures. Furthermore, we confirm the presence of four HGSOC transcriptional subtypes using a de novo classification. Survival differed statistically significantly between de novo subtypes (log rank, P = .006) and was the best for the immunoreactive-like subtype, but statistically significantly worse for the proliferative- or mesenchymal-like subtypes (adjusted hazard ratio = 1.89, 95% confidence interval = 1.18 to 3.02, P = .008, and adjusted hazard ratio = 2.45, 95% confidence interval = 1.43 to 4.18, P = .001, respectively). More prognostic information was provided by the de novo than the TCGA classification (Likelihood Ratio tests, P = .003 and P = .04, respectively). All statistical tests were two-sided. These findings were replicated in an external data set of 185 HGSOCs and confirm the presence of four prognostically relevant molecular subtypes that have the potential to guide therapy decisions.
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