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利用DNA微阵列分析探索川崎病患者对静脉注射免疫球蛋白反应相关的基因。

Exploring the genes associated with the response to intravenous immunoglobulin in patients with Kawasaki disease using DNA microarray analysis.

作者信息

Xing Yanlin, Wang Hong, Liu Xiaomei, Yu Xianyi, Chen Rui, Wang Ce, Yu Xuexin, Sun Le

机构信息

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China.

Experimental Research Center, Shengjing Hospital of China Medical University, Shenyang 110004, China.

出版信息

Exp Mol Pathol. 2015 Feb;98(1):7-12. doi: 10.1016/j.yexmp.2014.11.006. Epub 2014 Nov 14.

Abstract

In this study we aimed to screen genes associated with intravenous immunoglobulin (IVIG) responding in patients with Kawasaki disease (KD) and thus explore the underlying molecular mechanism of IVIG resistance. The differentially expressed genes (DEGs) were identified by samr package in R. Then, protein-protein interaction (PPI) networks were constructed by STRING software. We further collected the regulatory data from TRANSFAC database, followed by regulatory interaction network construction. A total 194 of DEGs, including 185 up- and 9 down-regulated DEGs, were identified between IVIG-responding and non-responding patients with KD at acute stage. In contrast, no DEGs were found at convalescent stage. PPI networks and regulatory networks were constructed based on the 185 up-regulated genes at acute stage. The degrees of TFRC (transferrin receptor protein 1) and GADD45A (growth arrest and DNA-damage-inducible alpha) were higher than other genes, and meanwhile MYC (V-Myc Myelocytomatosis Viral Oncogene Homolog) and E2F1 (E2F Transcription Factor 1) were found to be two TFs (transcription factors) with the highest degrees. In conclusions, the response to IVIG in Kawasaki disease patients may be involved in the expression of TFRC, GADD45A, MYC and E2F1.

摘要

在本研究中,我们旨在筛选与川崎病(KD)患者静脉注射免疫球蛋白(IVIG)反应相关的基因,从而探索IVIG抵抗的潜在分子机制。通过R语言中的samr软件包鉴定差异表达基因(DEG)。然后,使用STRING软件构建蛋白质-蛋白质相互作用(PPI)网络。我们进一步从TRANSFAC数据库收集调控数据,随后构建调控相互作用网络。在急性期,IVIG反应型和非反应型KD患者之间共鉴定出194个DEG,其中包括185个上调的DEG和9个下调的DEG。相比之下,在恢复期未发现DEG。基于急性期上调的185个基因构建了PPI网络和调控网络。转铁蛋白受体蛋白1(TFRC)和生长停滞及DNA损伤诱导α(GADD45A)的度数高于其他基因,同时发现原癌基因Myc(V-Myc髓细胞瘤病毒癌基因同源物)和E2F转录因子1(E2F1)是度数最高的两个转录因子(TF)。总之,川崎病患者对IVIG的反应可能与TFRC、GADD45A、MYC和E2F1的表达有关。

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