Department of Dermatology, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P.R. China.
Department of Burns, Plastic Surgery, Chengdu Military General Hospital, Chengdu, Sichuan 610083, P.R. China.
Mol Med Rep. 2014 Mar;9(3):1049-55. doi: 10.3892/mmr.2014.1908. Epub 2014 Jan 21.
The aim of the present study was to identify key genes associated with atopic dermatitis (AD) using microarray data and bioinformatic analyses. The dataset GSE6012, downloaded from the Gene Expression Omnibus (GEO) database, contains gene expression data from 10 AD skin samples and 10 healthy skin samples. Following data preprocessing, differentially expressed genes (DEGs) were identified using the limma package of the R project. Interaction networks were constructed comprising DEGs that showed a degree of node of >3, >5 and >10, using the Osprey software. Functional enrichment and pathway enrichment analysis of the network comprising all DEGs and of the network comprising DEGs with a high degree of node, were performed with the DAVID and WebGestalt toolkits, respectively. A total of 337 DEGs were identified. The functional enrichment analysis revealed that the list of DEGs was significantly enriched for proteins related to epidermis development (P=2.95E-07), including loricrin (LOR), keratin 17 (KRT17), small proline-rich repeat proteins (SPRRs) and involucrin (IVL). The chemokine signaling pathway was the most significantly enriched pathway (P=0.0490978) in the network of all DEGs and in the network consisting of high degree‑node DEGs (>10), which comprised the genes coding for chemokine receptor 7 (CCR7), chemokine ligand (CCL19), signal transducer and activator of transcription 1 (STAT1), and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1). In conclusion, the list of AD-associated proteins identified in this study, including LOR, KRT17, SPRRs, IVL, CCR7, CCL19, PIK3R1 and STAT1 may prove useful for the development of methods to treat AD. From these proteins, PIK3R1 and KRT17 are novel and promising targets for AD therapy.
本研究旨在使用微阵列数据和生物信息学分析鉴定与特应性皮炎(AD)相关的关键基因。从基因表达综合数据库(GEO)下载的数据集 GSE6012 包含 10 个 AD 皮肤样本和 10 个健康皮肤样本的基因表达数据。在数据预处理后,使用 R 项目中的 limma 包鉴定差异表达基因(DEG)。使用 Osprey 软件构建包含节点度>3、>5 和>10 的 DEG 的互作网络。使用 DAVID 和 WebGestalt 工具包分别对包含所有 DEG 的网络和包含高节点度 DEG 的网络进行功能富集和通路富集分析。共鉴定出 337 个 DEG。功能富集分析表明,DEG 列表显著富集与表皮发育相关的蛋白(P=2.95E-07),包括角蛋白 17(KRT17)、丝聚蛋白(LOR)、富含脯氨酸的小蛋白(SPRRs)和内披蛋白(IVL)。趋化因子信号通路是所有 DEG 网络和高节点度 DEG(>10)网络中最显著富集的通路(P=0.0490978),包含趋化因子受体 7(CCR7)、趋化因子配体(CCL19)、信号转导和转录激活因子 1(STAT1)和磷脂酰肌醇-3-激酶调节亚基 1(PIK3R1)的基因。总之,本研究中鉴定的与 AD 相关的蛋白,包括 LOR、KRT17、SPRRs、IVL、CCR7、CCL19、PIK3R1 和 STAT1,可能有助于开发治疗 AD 的方法。从这些蛋白中,PIK3R1 和 KRT17 是 AD 治疗的新的有前途的靶点。