Prognostic and Therapeutic Relevance of Molecular Subtypes in High-Grade Serous Ovarian Cancer
Prognostic and Therapeutic Relevance of Molecular Subtypes in High-Grade Serous Ovarian Cancer
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DOI：
10.1093/jnci/dju249
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发表时间：
2014-10-01
影响因子：
10.3
通讯作者：
Goode, Ellen L.
中科院分区：
文献类型：
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作者：
Konecny, Gottfried E.;Wang, Chen;Goode, Ellen L.
使用转录谱对高级别浆液性卵巢癌（HGSOC）进行分子分类已被证明是复杂的，并且难以在研究中验证。我们确定了174个注释良好的HGSOC的基因表达谱，并证明了预先指定的TCGA网络基因签名的预后意义。此外，我们确认存在四个HGSOC转录亚型使用从头分类。新发亚型之间的生存率差异具有统计学意义（对数秩，P = 0.006），免疫反应性样亚型最好，但增殖或间质样亚型统计学显著较差（调整后的风险比= 1.89，95%置信区间= 1.18至3.02，P = 0.008，调整后的风险比= 2.45，95%置信区间= 1.43至4.18，P = 0.001，分别）。与TCGA分类相比，从头分类提供了更多的预后信息（Likewise Ratio检验，分别为P = 0.003和P = 0.04）。所有统计学检验均为双侧检验。这些发现在185个HGSOC的外部数据集中得到了复制，并证实了存在四种可能指导治疗决策的临床相关分子亚型。
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.