Efficient molecular subtype classification of high-grade serous ovarian cancer
Efficient molecular subtype classification of high-grade serous ovarian cancer
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DOI：
10.1002/path.4536
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发表时间：
2015-07-01
影响因子：
7.3
通讯作者：
Bowtell, David
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文献类型：
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作者：
Leong, Huei San;Galletta, Laura;Bowtell, David
高级别浆液性癌（HGSC）约占所有诊断的上皮性卵巢癌的70%。使用微阵列基因表达谱，我们以前确定了HGSC的四种分子亚型：C1（间充质），C2（免疫反应性），C4（分化）和C5（增殖），这与患者的生存相关，并具有独特的生物学特征。在这里，我们描述了基于有限数量的基因的HGSC的分子分类，以允许成本效益和高通量亚型分析。我们确定了一个最小的签名，准确的分类，包括39个差异表达和9个控制基因的微阵列实验。然后比较基于Taqman的（低密度阵列和Fluidigm）、荧光寡核苷酸（Nanostring）和靶向RNA测序（Illumina）测定正确分类新鲜和福尔马林固定的石蜡包埋样品的能力。所有平台对来自新鲜冷冻样品的RNA均实现>90%的分类准确度。Illumina和Nanostring试验在固定材料的情况下具有上级优势。我们发现C1、C2和C4分子亚型在来自个体化疗初治患者的多种手术沉积物中基本一致。相比之下，我们在原发卵巢样本分类为C5的患者中观察到大量的亚型异质性。HGSC的有效分子分类器的开发将使分子亚型的进一步生物学表征和靶向临床试验的发展成为可能。版权所有（c）2015大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
High-grade serous carcinomas (HGSCs) account for approximately 70% of all epithelial ovarian cancers diagnosed. Using microarray gene expression profiling, we previously identified four molecular subtypes of HGSC: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative), which correlate with patient survival and have distinct biological features. Here, we describe molecular classification of HGSC based on a limited number of genes to allow cost-effective and high-throughput subtype analysis. We determined a minimal signature for accurate classification, including 39 differentially expressed and nine control genes from microarray experiments. Taqman-based (low-density arrays and Fluidigm), fluorescent oligonucleotides (Nanostring), and targeted RNA sequencing (Illumina) assays were then compared for their ability to correctly classify fresh and formalin-fixed, paraffin-embedded samples. All platforms achieved>90% classification accuracy with RNA from fresh frozen samples. The Illumina and Nanostring assays were superior with fixed material. We found that the C1, C2, and C4 molecular subtypes were largely consistent across multiple surgical deposits from individual chemo-naive patients. In contrast, we observed substantial subtype heterogeneity in patients whose primary ovarian sample was classified as C5. The development of an efficient molecular classifier of HGSC should enable further biological characterization of molecular subtypes and the development of targeted clinical trials. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.