Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis
Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis
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DOI：
10.1093/carcin/bgt208
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发表时间：
2013-10-01
期刊：
影响因子：
4.7
通讯作者：
Clynes, Martin
中科院分区：
文献类型：
--
作者：
Clarke, Colin;Madden, Stephen F.;Clynes, Martin
加权基因共表达网络分析(WGCNA)是一种强大的基于关联内疚的方法，可以从大规模的异质信使RNA表达数据集中提取共表达的基因组。我们利用WGCNA从13个基于微阵列的基因表达研究中识别了2342个乳腺癌样本中的11个共调控基因簇。这些转录模块中的许多被发现与临床病理变量(例如，肿瘤分级)、整个乳腺癌的生存终点(无病生存、远地无病生存和总体生存)以及其分子亚型(腔A、腔B、HER2和基底样)相关。这项工作产生的发现的例子包括识别出一组与增殖相关的基因，当上调时，这些基因与肿瘤分级的增加相关，并与总体上较差的存活率相关。一个独立的数据集证实了这一组中新基因的预后潜力，例如泛素结合酶E2S(UBE2S)。此外，基因簇还与乳腺癌分子亚型的存活率相关，包括被发现仅与基底细胞样乳腺癌预后相关的一组基因。在这个共表达簇中，几个单基因的上调，例如钾通道，K亚家族成员5(KCNK5)，与基底样分子亚型的不良结局相关。我们已经开发了一个在线数据库，允许用户友好地访问本研究中发现的共表达模式和生存分析输出(可访问)。
Weighted gene coexpression network analysis (WGCNA) is a powerful guilt-by-association-based method to extract coexpressed groups of genes from large heterogeneous messenger RNA expression data sets. We have utilized WGCNA to identify 11 coregulated gene clusters across 2342 breast cancer samples from 13 microarray-based gene expression studies. A number of these transcriptional modules were found to be correlated to clinicopathological variables (e.g. tumor grade), survival endpoints for breast cancer as a whole (disease-free survival, distant disease-free survival and overall survival) and also its molecular subtypes (luminal A, luminal B, HER2 and basal-like). Examples of findings arising from this work include the identification of a cluster of proliferation-related genes that when upregulated correlated to increased tumor grade and were associated with poor survival in general. The prognostic potential of novel genes, for example, ubiquitin-conjugating enzyme E2S (UBE2S) within this group was confirmed in an independent data set. In addition, gene clusters were also associated with survival for breast cancer molecular subtypes including a cluster of genes that was found to correlate with prognosis exclusively for basal-like breast cancer. The upregulation of several single genes within this coexpression cluster, for example, the potassium channel, subfamily K, member 5 (KCNK5) was associated with poor outcome for the basal-like molecular subtype. We have developed an online database to allow user-friendly access to the coexpression patterns and the survival analysis outputs uncovered in this study (available at ).