Key regulators in prostate cancer identified by co-expression module analysis.
Key regulators in prostate cancer identified by co-expression module analysis.
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通过共表达模块分析确定前列腺癌的关键调节因子。
DOI：
10.1186/1471-2164-15-1015
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发表时间：
2014-11-24
期刊：
影响因子：
4.4
通讯作者：
Shen B
中科院分区：
文献类型：
--
作者：
Jiang J;Jia P;Zhao Z;Shen B
前列腺癌(PrCa)是世界上最常见的男性癌症。尽管已对其大量基因进行了研究，但其病因仍知之甚少。此外，大多数PrCa候选基因还没有被严格复制，它们在PrCa中发挥生物学功能的方法在很大程度上仍不清楚。为了识别复杂的前列腺癌系统中的关键角色，我们重建了由基因本体论(GO)注释(生物学过程，GO_BP)定义的功能基因集中的PrCa共表达模块。我们初步确定了118个GO_BP术语，这些术语在两个独立的基因表达数据集之间保存得很好，从而在它们之间有55个保守的共表达模块。然后，从表达数量性状基因座(EQTL)、体细胞拷贝数改变(SCNA)、体细胞突变数据或预后分析中收集的PrCa候选基因被发现显著丰富了五个模块。具体地说，调控这五个候选模块的两个转录因子(TF)(NFAT和SP1)和三个microRNAs(hsa-miR-19a、hsa-miR-15a和hsa-miR-200b)对PrCa的发育至关重要。总之，我们的结果表明，功能相似的基因可能通过共表达在疾病中发挥重要作用，而不同功能的模块可能会受到相似的遗传成分的协同调节，如转录因子和microRNAs。本文的在线版本(DOI：10.1186/1471-2164-15-1015)包含补充材料，授权用户可以使用。
Prostate cancer (PrCa) is the most commonly diagnosed cancer in men in the world. Despite the fact that a large number of its genes have been investigated, its etiology remains poorly understood. Furthermore, most PrCa candidate genes have not been rigorously replicated, and the methods by which they biologically function in PrCa remain largely unknown. Aiming to identify key players in the complex prostate cancer system, we reconstructed PrCa co-expressed modules within functional gene sets defined by the Gene Ontology (GO) annotation (biological process, GO_BP). We primarily identified 118 GO_BP terms that were well-preserved between two independent gene expression datasets and a consequent 55 conserved co-expression modules within them. Five modules were then found to be significantly enriched with PrCa candidate genes collected from expression Quantitative Trait Loci (eQTL), somatic copy number alteration (SCNA), somatic mutation data, or prognostic analyses. Specifically, two transcription factors (TFs) (NFAT and SP1) and three microRNAs (hsa-miR-19a, hsa-miR-15a, and hsa-miR-200b) regulating these five candidate modules were found to be critical to the development of PrCa. Collectively, our results indicated that genes with similar functions may play important roles in disease through co-expression, and modules with different functions could be regulated by similar genetic components, such as TFs and microRNAs, in a synergistic manner. The online version of this article (doi:10.1186/1471-2164-15-1015) contains supplementary material, which is available to authorized users.
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DOI：
10.1073/pnas.97.1.262
发表时间：
2000-01-04
影响因子：
11.1
作者：
Brown, MPS;Grundy, WN;Haussler, D
通讯作者：
Haussler, D
影响因子：
11
作者：
Chen, C.;Cheng, L.;Grennan, K.;Pibiri, F.;Zhang, C.;Badner, J. A.;Gershon, E. S.;Liu, C.
通讯作者：
Liu, C.
影响因子：
4.5
作者：
Choy E;Yelensky R;Bonakdar S;Plenge RM;Saxena R;De Jager PL;Shaw SY;Wolfish CS;Slavik JM;Cotsapas C;Rivas M;Dermitzakis ET;Cahir-McFarland E;Kieff E;Hafler D;Daly MJ;Altshuler D
通讯作者：
Altshuler D
DOI：
10.1073/pnas.1200853109
发表时间：
2012-07-10
影响因子：
11.1
作者：
Grisanzio, Chiara;Werner, Lillian;Freedman, Matthew L.
通讯作者：
Freedman, Matthew L.
影响因子：
82.9
作者：
Bonci, Desiree;Coppola, Valeria;De Maria, Ruggero
通讯作者：
De Maria, Ruggero