Smoking and drinking influence the advancing of ischemic stroke disease by targeting PTGS2 and TNFAIP3

Abstract

In the present study, we explored the influence of cigarette smoking and alcohol drinking on gene expression level and related functions and pathways on the development of ischemic stroke (IS) disease. The gene expression profile of E-GEOD-22255 was obtained from 20 IS samples (7 patients without smoking or drinking history and 13 patients with smoking or drinking history) and 20 controls (9 normal controls without smoking or drinking history and 11 controls with smoking or drinking history). The correlation degree between gene expression and grouping were measured by significance analysis of microarray (SAM). Smoking or drinking-related DEGs were screened. GO functional and KEGG pathway enrichment analyses were processed. Based on the KEGG database, a pathway relationship network was constructed. DEGs in significant functions and pathways were inserted and regarded as key DEGs. Gene co-expression network was constructed based on the expression value of key genes. In total, 319 IS-related DEGs, which were induced by smoking and drinking, were screened and enriched in various functions and pathways, including inflammatory response, nuclear factor-κB (NF-κB) signaling pathway and influenza A. Pathway relationship network was constructed with 44 nodes and the hub node was the MAPK signaling pathway. After merging, 87 key DEGs were obtained. The gene co-expression network with 43 node edges was constructed and the hub node was prostaglandin-endoperoxide synthase 2. In IS patients, smoking and drinking may induce different expression of many genes, including PTGS2, TNFAIP3, ZFP36 and NFKBIZ. In addition, these genes participated in various pathways, such as inflammatory response.

Keywords: biomarker; genomic expression profile; ischemic stroke; smoking and drinking history.

Figure 1.

Pathway relationship network. The nodes represent pathways enriched by special DEGs, and the arrows represent regulatory relationship. The size of nodes was determined by degree. The red nodes represent pathways with upregulated genes, while the yellow nodes represent pathways with both upregulated and downregulated genes.

Figure 2.

Gene co-expression network of key special DEGs. The nodes are key special DEGs. Solid and dotted lines show the relationship of positive and negative regulation, respectively.