Time course analysis based on gene expression profile and identification of target molecules for colorectal cancer.
Time course analysis based on gene expression profile and identification of target molecules for colorectal cancer.
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基于基因表达谱的时程分析和结直肠癌靶分子的鉴定。
DOI：
10.1186/s12935-016-0296-3
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发表时间：
2016
影响因子：
5.8
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Chen G;Han N;Li G;Li X;Li G;Li Z;Li Q
本研究旨在探讨大肠癌中基因表达的变化，筛选潜在的分子靶点。从Gene Expression Omnibus数据库下载GSE 37178的mRNA表达谱，包括通过手术切除提取的CRC样品和配对的正常样品。筛选在4个不同时间点表达发生变化的基因，并使用Mfuzz软件包进行聚类。然后利用大卫对不同簇中的基因进行功能和途径富集分析。根据STRING数据库构建了簇中基因的蛋白质相互作用（PPI）网络。在此基础上，根据数据库中的资源，获得相关转录因子（TF）和microRNA（miRNAs），并与每个聚类中的PPI网络相结合，构建包含基因、TF和miRNAs的整合网络。结果，314个基因被聚成四个组。聚类1和聚类2中的基因呈下降趋势，聚类3和聚类4中的基因呈上升趋势。然后是18个TF（例如，TCF 4、MEF 2C和FOS）和18种miRNA（例如，miR-382、miR-217、miR-1184、miR-326和miR-330- 5 p），并构建了簇1、3和4的三个整合网络。结果提示，PITX 2、VSNL 1、TCF 4、MEF 2C和FOS的表达与时间相关，并伴随miR-382、miR-217、miR-21、miR-1184、miR-326和miR-330- 5 p等多种miRNA的表达。它们都有可能成为大肠癌潜在的诊断或治疗靶分子。
The study aimed to investigate the expression changes of genes in colorectal cancer (CRC) and screen the potential molecular targets. The GSE37178 of mRNA expression profile including the CRC samples extracted by surgical resection and the paired normal samples was downloaded from Gene Expression Omnibus database. The genes whose expressions were changed at four different time points were screened and clustered using Mfuzz package. Then DAVID was used to perform the functional and pathway enrichment analysis for genes in different clusters. The protein–protein interaction (PPI) networks were constructed for genes in the clusters according to the STRING database. Furthermore, the related-transcription factors (TFs) and microRNAs (miRNAs) were obtained based on the resources in databases and then were combined with the PPI networks in each cluster to construct the integrated network containing genes, TFs and miRNAs. As a result, 314 genes were clustered into four groups. Genes in cluster 1 and cluster 2 showed a decreasing trend, while genes in cluster 3 and cluster 4 presented an increasing trend. Then 18 TFs (e.g., TCF4, MEF2C and FOS) and 18 miRNAs (e.g., miR-382, miR-217, miR-1184, miR-326 and miR-330-5p) were identified and three integrated networks for cluster 1, 3, and 4 were constructed. The results implied that expression of PITX2, VSNL1, TCF4, MEF2C and FOS are time-related and associated with CRC development, accompanied by several miRNAs including miR-382, miR-217, miR-21, miR-1184, miR-326 and miR-330-5p. All of them might be used as potential diagnostic or therapeutic target molecules for CRC.