Prognostic and Therapeutic Relevance of Molecular Subtypes in High-Grade Serous Ovarian Cancer

作者：Gottfried E. Konecny, Chen Wang, Habib Hamidi, Boris J. N. Winterhoff, Kimberly R. Kalli, Judy Dering, Charles Ginther, Hsiao‐Wang Chen, Sean Christopher Dowdy, William A. Cliby, Bobbie S. Gostout, Karl C. Podratz, Gary L. Keeney, He-Jing Wang, Lynn C. Hartmann, Dennis J. Slamon, Ellen L. Goode · 发表于：JNCI Journal of the National Cancer Institute · 年份：2014 · DOI：10.1093/jnci/dju249 · 被引用次数：416 · 研究领域：Ovarian cancer diagnosis and treatment、Cancer-related molecular mechanisms research、RNA modifications and cancer

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.