Long Fei, Wang Ling, Yang Lei, Ji Zhou, Hu YaGuang
The Third Affiliated Hospital of Jinzhou Medical University.
Cardiol J. 2018;25(3):403-411. doi: 10.5603/CJ.a2017.0106. Epub 2017 Oct 5.
Coronary artery disease (CAD) is the leading cause of mortality worldwide. Identifying key pathogenic genes benefits the understanding molecular mechanism of CAD.
In this study, 5 microarray data sets from the blood sample of 312 CADs and 277 healthy controls were downloaded. Limma and metaMA packages were used to identify differentially expressed genes. The functional enrichment analysis of differentially expressed genes was further performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Additionally, protein-protein interac-tion and transcript factors-target networks were performed based on top 10 up- and down-regulated differentially expressed genes to further study the biological function. Last, real-time quantitative poly-merase chain reaction (RT-qPCR) was used to validate the integrated analysis result.
A total of 528 differentially expressed genes were obtained. All differentially expressed genes were significantly involved in signal transduction and the MAPK signaling pathway. Among MAPK signaling pathway, IL1R2, ARRB2 and PRKX were associated with CAD. Furthermore, there were 4 common differentially expressed genes including PLAUR, HSPH1, ZMYND11 and S100A8 in the protein-protein interaction and transcript factors-target networks, which played crucial roles in the development of CAD. In quantitative RT-qPCR, the expression of PRKX, HSPH1 and ZMYND11 was down-regulated and consistent with the integrated analysis.
Identified 7 differentially expressed genes (IL1R2, ARRB2, PRKX, PLAUR, HSPH1, ZMYND11 and S100A8) may play crucial roles in the development of CAD.
冠状动脉疾病（CAD）是全球范围内导致死亡的主要原因。识别关键致病基因有助于理解CAD的分子机制。
在本研究中，下载了来自312例CAD患者和277例健康对照者血液样本的5个微阵列数据集。使用Limma和metaMA软件包来识别差异表达基因。通过基因本体论和京都基因与基因组百科全书对差异表达基因进行功能富集分析。此外，基于上调和下调排名前10的差异表达基因构建蛋白质-蛋白质相互作用和转录因子-靶标网络，以进一步研究其生物学功能。最后，使用实时定量聚合酶链反应（RT-qPCR）验证综合分析结果。
共获得528个差异表达基因。所有差异表达基因均显著参与信号转导和MAPK信号通路。在MAPK信号通路中，IL1R2、ARRB2和PRKX与CAD相关。此外，在蛋白质-蛋白质相互作用和转录因子-靶标网络中有4个共同的差异表达基因，包括PLAUR、HSPH1、ZMYND11和S100A8，它们在CAD的发生发展中起关键作用。在定量RT-qPCR中，PRKX、HSPH1和ZMYND11的表达下调，与综合分析结果一致。
鉴定出的7个差异表达基因（IL1R2、ARRB2、PRKX、PLAUR、HSPH1、ZMYND11和S100A8）可能在CAD的发生发展中起关键作用。
