细胞间黏附分子-1基因在冠心病中的生物学功能以及冠心病初级调控网络建立:一项基于文献的二次分析

Biological function of intercellular adhesion molecule-1 gene in coronary heart disease and its mediated primary regulatory network: a literature based secondary analysis

目的探讨细胞间黏附分子-1(ICAM-1)基因在冠心病(CHD)中的生物学功能及CHD初级调控网络建立。方法检索万方数据库、中国期刊全文数据库(CNKI)、维普数据库、Google学术、PubMed数据库等,2006年1月1日至2018年12月31日公开发表的关于CHD基因ICAM-1临床研究的中英文文献,试验组为CHD患者,对照组为健康人群,采用Meta分析探讨ICAM-1与CHD的关系。随后利用基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路数据库分别对ICAM-1基因进行功能注释及通路分析。结果检索数据库共纳入8篇文献,Meta分析结果显示,试验组ICAM-1水平显著高于对照组〔均数差(MD)=15.29,95%可信区间(95%CI)=10.95~19.62,P<0.00001〕,表明ICAM-1与CHD显著相关。GO分析结果显示,ICAM-1分子功能主要涉及病毒受体活性、受体活性、跨膜信号受体活性、蛋白结合等;细胞组分主要涉及质膜积分成分、免疫突触、质膜等;生物过程主要涉及细胞黏附、白细胞黏附、白细胞迁移、白细胞黏附的正向调节等。此外,结合KEGG通路数据库成功绘制出ICAM-1介导的CHD初级调控网络图,可知,ICAM-1主要在内皮细胞中表达,进而通过促进白细胞的增殖,调节CHD的发生发展。结论ICAM-1可能通过调节白细胞的相关生物过程进而调节CHD的发生发展。成功建立ICAM-1介导的CHD调控网络,可为进一步探讨ICAM-1及其他相关基因在CHD发生中的具体调控作用奠定理论基础。

Objective To explore the biological function of intercellular adhesion molecule-1 (ICAM-1) gene in coronary heart disease (CHD) and to establish a primary regulatory network mediated by ICAM-1 gene. Methods The databases were searched from January 1st 2006 to December 31st 2018, including Wanfang, CNKI, VIP, Google scholar and PubMed databases for published researches on clinical study of CHD gene ICAM-1. The experimental group was CHD patients, and the control group was healthy people. Meta-analysis was employed to analyze the relationship between ICAM-1 gene and CHD. Gene Ontology (GO) and KEGG Pathway database were employed to conduct function annotation and pathway analysis. Results A total of 8 papers were enrolled into this analysis, Meta-analysis showed that the level of ICAM-1 in the experimental group was significantly higher than that in the control group [mean difference (MD)= 15.29, 95% confidence interval (95%CI)= 10.95-19.62, P < 0.000?01], surface ICAM-1 was significantly related with CHD. The GO analysis results showed that ICAM-1 molecular function mainly involved virus receptor activity, receptor activity, transmembrane signal receptor activity, protein binding, etc.;cell components mainly involve plasma membrane integral components, immune synapses, plasma membrane, etc.;biological processes mainly involve the positive regulation of cell adhesion, leukocyte adhesion, leukocyte migration and leukocyte adhesion, etc. A primary CHD regulatory network mediated by ICAM-1 gene was established based on KEGG Pathway database, and ICAM-1 was mainly expressed in endothelial cells, and further regulated the occurrence and development of CHD by promoting the proliferation of leukocytes. Conclusions ICAM-1 may regulate the occurrence and development of CHD by regulating the related biological processes of leukocytes. The successful establishment of the ICAM-1 mediated CHD regulatory network can lay a theoretical foundation for further exploring the specific regulatory role of ICAM-1 and other related genes in CHD occurrence.