Identification of novel candidate genes involved in the progression of emphysema by bioinformatic methods

Abstract

PurposeBy reanalyzing the gene expression profile GSE76925 in the Gene Expression Omnibus database using bioinformatic methods, we attempted to identify novel candidate genes promoting the development of emphysema in patients with COPD.Patients and methodsAccording to the Quantitative CT data in GSE76925, patients were divided into mild emphysema group (%LAA-950<20%, n=12) and severe emphysema group (%LAA-950>50%, n=11). Differentially expressed genes (DEGs) were identified using Agilent GeneSpring GX v11.5 (corrected P-value <0.05 and |Fold Change|>1.3). Known driver genes of COPD were acquired by mining literatures and retrieving databases. Direct protein–protein interaction network (PPi) of DEGs and known driver genes was constructed by STRING.org to screen the DEGs directly interacting with driver genes. In addition, we used STRING.org to obtain the first-layer proteins interacting with DEGs’ products and constructed the indirect PPi of these interaction proteins. By merging the indirect PPi with driver genes’ PPi using Cytoscape v3.6.1, we attempted to discover potential pathways promoting emphysema’s development.ResultsAll the patients had COPD with severe airflow limitation (age=62±8, FEV1%=28±12). A total of 57 DEGs (including 12 pseudogenes) and 135 known driving genes were identified. Direct PPi suggested that GPR65, GNB4, P2RY13, NPSR1, BCR, BAG4, and IMPDH2 were potential pathogenic genes. GPR65 could regulate the response of immune cells to the acidic microenvironment, and NPSR1’s expression on eosinophils was associated with asthma’s severity and IgE level. Indirect merging PPi demonstrated that the interacting network of TP53, IL8, CCR2, HSPA1A, ELANE, PIK3CA was associated with the development of emphysema. IL8, ELANE, and PIK3CA were molecules involved in the pathological mechanisms of emphysema, which also in return proved the role of TP53 in emphysema.ConclusionCandidate genes such as GPR65, NPSR1, and TP53 may be involved in the progression of emphysema.

Variable Expressed Methylation Sites of Aging-related Genes in Asthma

“…Similarly, TP53 has been shown to be involved in the progression of COPD by mediating the senescence of multiple lung cells [36]. It has also shown that TP53 is overexpressed in emphysema tissues, which can promote the progression of emphysema in COPD patients [33].…”

“…Many studies have demonstrated the exist of aging structural cells, immune cells and mesenchymal cells in asthmatic lung although the speci c role of aging cells in asthma is still not fully understood [20,30,31]. Meanwhile, some related studies have also con rmed the different expression of aging-related genes (such as TP53 and FOXO3) in the development of respiratory diseases [32,33]. The polymorphism of transcription factor FOXO3 has been shown to be involved in the overactivation of mast cells, down-regulation of antiin ammatory factors and production of cytokines during the pathogenesis of COPD and asthma [34].…”

Variable expressed methylation sites of aging-related genes in asthma

“…Many studies have demonstrated the exist of aging structural cells, immune cells and mesenchymal cells in asthmatic lung although the speci c role of aging cells in asthma is still not fully understood [20,30,31]. Meanwhile, some related studies have also con rmed the different expression of aging-related genes (such as TP53 and FOXO3) in the development of respiratory diseases [32,33]. The polymorphism of transcription factor FOXO3 has been shown to be involved in the overactivation of mast cells, down-regulation of anti-in ammatory factors and production of cytokines during the pathogenesis of COPD and asthma [34].…”

Identification of differentially expressed genes and enriched pathways in lung cancer using bioinformatics analysis

“…There were 120 chips in this dataset. Following quality control by signal strength distribution normalization, correlation analysis and principal component analysis in Agilent Gene-Spring GX v.11.5 (14), the mismatched ones were eliminated and the remaining 31 pairs of cancerous and normal tissues were used for subsequent analysis.…”