Validated gene targets associated with curatively treated advanced serous ovarian carcinoma
Validated gene targets associated with curatively treated advanced serous ovarian carcinoma
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DOI：
10.1016/j.ygyno.2012.11.018
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发表时间：
2013-03-01
影响因子：
4.7
通讯作者：
Levine, Douglas A.
中科院分区：
文献类型：
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作者：
Barlin, Joyce N.;Jelinic, Petar;Levine, Douglas A.
目的。高级别浆液性卵巢癌（HGSOC）大多在晚期才被发现，总体生存率较低。然而，有一部分患者在标准的初始治疗后似乎被治愈。我们假设这些患者的分子特征与复发的长期存活者不同。
方法。从癌症基因组图谱（TCGA）和机构（纪念斯隆 - 凯特琳癌症中心，MSKCC）样本中确定了接受初次肿瘤细胞减灭术和铂类化疗的晚期HGSOC患者。治愈意向组定义为无复发生存期>5年。长期复发组由复发但存活>5年的患者组成。RNA与Affymetrix U133A转录微阵列进行杂交。NanoString nCounter基因表达系统用于在独立的患者群体中进行验证。
结果。在30名治愈患者和84名复发患者中，类别比较发现两组之间差异表达的探针数量是仅凭偶然预期数量的两倍。TCGA和MSKCC数据集有19个重叠基因。通路分析确定了过度代表的网络，包括核因子κB（NFκB）转录和细胞外信号调节激酶（ERK）信号传导。在28名治愈患者和38名复发患者的独立人群中进行了外部验证。我们原始数据集之间共有的三个基因（CYP4B1、CEPT1、CHMP4A）在外部验证数据中仍然差异表达。
结论。在可能通过标准初始治疗治愈的HGSOC患者中存在独特的转录元件。三个基因经受住了严格的验证，是进一步研究的合理靶点，这可能为长期生存相关的分子特征和化疗耐药机制提供见解。（C）2012爱思唯尔公司。保留所有权利。
Objectives. High-grade serous ovarian cancer (HGSOC) mostly presents at an advanced stage and has a low overall survival rate. However, a subgroup of patients are seemingly cured after standard initial therapy. We hypothesize that the molecular profiles of these patients vary from long-term survivors who recur.Methods. Patients with advanced HGSOC who underwent primary cytoreductive surgery and platinum-based chemotherapy were identified from The Cancer Genome Atlas (TCGA) and institutional (MSKCC) samples. A curative-intent group was defined by recurrence-free survival of >5 years. A long-term recurrent group was composed of patients who recurred but survived >5 years. RNA was hybridized to Affymetrix U133A transcription microarrays. The NanoString nCounter gene expression system was used for validation in an independent patient population.Results. In 30 curative and 84 recurrent patients, class comparison identified twice as many differentially expressed probes between the groups than expected by chance alone. TCGA and MSKCC data sets had 19 overlapping genes. Pathway analyses identified over-represented networks that included nuclear factor kappa B (NFkB) transcription and extracellular signal-regulated kinase (ERK) signaling. External validation was performed in an independent population of 28 curative and 38 recurrent patients. Three genes (CYP4B1, CEPT1, CHMP4A) in common between our original data sets remained differentially expressed in the external validation data.Conclusions. There are distinct transcriptional elements in HGSOC from patients likely to be cured by standard primary therapy. Three genes have withstood rigorous validation and are plausible targets for further study, which may provide insight into molecular features associated with long-term survival and chemotherapy resistance mechanisms. (C) 2012 Elsevier Inc. All rights reserved.