Prognostically relevant gene signatures of high-grade serous ovarian carcinoma
Prognostically relevant gene signatures of high-grade serous ovarian carcinoma
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DOI：
10.1172/jci65833
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发表时间：
2013-01-01
影响因子：
15.9
通讯作者：
Meyerson, Matthew
中科院分区：
文献类型：
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作者：
Verhaak, Roel G. W.;Tamayo, Pablo;Meyerson, Matthew
由于高级别浆液性卵巢癌（HGS-OvCa）的复发风险较高，因此结局预测因子的开发对患者分层可能有价值。使用癌症基因组图谱（TCGA）的目录，我们开发了亚型和存活基因表达特征，当其组合时，提供了HGS-OvCa分类的预后模型，称为“卵巢癌分类”（CLOVAR）。我们在由879个HGS-OvCa表达谱组成的独立数据集上验证了CLOVAR。最差结局组占所有病例的23%，中位生存期为23个月，铂类耐药率为63%，而其他病例的中位生存期为46个月，铂类耐药率为23%。将结果预测模型与BRCA 1/BRCA 2突变状态、术后残留疾病和疾病分期相关联，进一步优化了结果分类。卵巢癌是一种急需更有效治疗的疾病。这里观察到的结果谱及其与CLOVAR特征的关联表明了潜在肿瘤生物学的变化。在其他预后变量的背景下对CLOVAR模型的前瞻性验证可能为患者和治疗方案的最佳组合提供依据。
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.