Integrated DNA Copy Number and Gene Expression Regulatory Network Analysis of Non-small Cell Lung Cancer Metastasis
Integrated DNA Copy Number and Gene Expression Regulatory Network Analysis of Non-small Cell Lung Cancer Metastasis
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DOI：
10.4137/cin.s14055
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发表时间：
2014-01-01
影响因子：
2
通讯作者：
Guo, Nancy
中科院分区：
文献类型：
--
作者：
Iranmanesh, Seyed;Guo, Nancy
在癌症易感性和转移分析中，多水平分子谱的综合分析可以区分基于一类数据不能揭示的相互作用。DNA拷贝数变异（CNVs）在癌细胞中很常见，它们在细胞行为中的作用以及与基因表达（GE）的关系知之甚少。CNV和全基因组mRNA表达的综合分析可以发现拷贝数的改变及其对GE的可能调控作用。该研究为识别重要基因和构建基于这些基因的潜在调控网络提供了一个新的框架。使用这种方法，DNA拷贝数畸变及其对GE在肺癌进展中的影响被揭示。具体地，该方法包括以下步骤：（1）选择在肺癌患者肿瘤中具有显著CNV或在转录水平上与临床结果具有显著关联的候选驱动基因库;（2）将肺癌患者中的重要驱动基因分别排列为预后良好和预后不良，并使用排名靠前的驱动基因，通过COPYNumber and EXPRESSION IN Cancer（CONEXIC）方法构建调控网络：（3）使用不相容性通路分析（IPA）鉴定所构建调控网络中实验证实的分子相互作用;（4）用Genatomy软件包可视化精细化的调控网络。构建的CNV/mRNA调控网络为研究肺癌转移中CNV调控的转录机制提供了重要的信息。
Integrative analysis of multi-level molecular profiles can distinguish interactions that cannot be revealed based on one kind of data in the analysis of cancer susceptibility and metastasis. DNA copy number variations (CNVs) are common in cancer cells, and their role in cell behaviors and relationship to gene expression (GE) is poorly understood. An integrative analysis of CNV and genome-wide mRNA expression can discover copy number alterations and their possible regulatory effects on GE. This study presents a novel framework to identify important genes and construct potential regulatory networks based on these genes. Using this approach, DNA copy number aberrations and their effects on GE in lung cancer progression were revealed. Specifically, this approach contains the following steps: (1) select a pool of candidate driver genes, which have significant CNV in lung cancer patient tumors or have a significant association with the clinical outcome at the transcriptional level; (2) rank important driver genes in lung cancer patients with good prognosis and poor prognosis, respectively, and use top-ranked driver genes to construct regulatory networks with the COpy Number and EXpression In Cancer (CONEXIC) method; (3) identify experimentally confirmed molecular interactions in the constructed regulatory networks using Ingenuity Pathway Analysis (IPA); and (4) visualize the refined regulatory networks with the software package Genatomy. The constructed CNV/mRNA regulatory networks provide important insights into potential CNV-regulated transcriptional mechanisms in lung cancer metastasis.