Comprehensive analysis of endoplasmic reticulum stress-associated genes signature of ulcerative colitis

Abstract

BackgroundEndoplasmic reticulum stress (ERS) is a critical factor in the development of ulcerative colitis (UC); however, the underlying molecular mechanisms remain unclear. This study aims to identify pivotal molecular mechanisms related to ERS in UC pathogenesis and provide novel therapeutic targets for UC.MethodsColon tissue gene expression profiles and clinical information of UC patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database, and the ERS-related gene set was downloaded from GeneCards for analysis. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were utilized to identify pivotal modules and genes associated with UC. A consensus clustering algorithm was used to classify UC patients. The CIBERSORT algorithm was employed to evaluate the immune cell infiltration. Gene Set Variation Analysis (GSVA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore potential biological mechanisms. The external sets were used to validate and identify the relationship of ERS-related genes with biologics. Small molecule compounds were predicted using the Connectivity Map (CMap) database. Molecular docking was performed to simulate the binding conformation of small molecule compounds and key targets.ResultsThe study identified 915 differentially expressed genes (DEGs) and 11 ERS-related genes (ERSRGs) from the colonic mucosa of UC patients and healthy controls, and these genes had good diagnostic value and were highly correlated. Five potential small-molecule drugs sharing tubulin inhibitors were identified, including albendazole, fenbendazole, flubendazole, griseofulvin, and noscapine, among which noscapine exhibited the highest correlation with a high binding affinity to the targets. Active UC and 10 ERSRGs were associated with a large number of immune cells, and ERS was also associated with colon mucosal invasion of active UC. Significant differences in gene expression patterns and immune cell infiltration abundance were observed among ERS-related subtypes.ConclusionThe results suggest that ERS plays a vital role in UC pathogenesis, and noscapine may be a promising therapeutic agent for UC by affecting ERS.

Comprehensive Analysis of Key Endoplasmic Reticulum Stress-Related Genes and Immune Infiltrates in Stanford Type A Aortic Dissection

“…Following the methods reported in the previous literature, 21 we downloaded the ERSRGs from the GeneCards website, obtaining 1350 genes. These genes were intersected with differential genes obtained by GSE52093 to obtain differentially expressed ERSRGs in TAAD.…”

Identifying hub genes in response to ustekinumab and the impact of ustekinumab treatment on fibrosis in Crohn’s disease

“…To identify the clinical characteristics, we created a topological overlap matrix (TOM) containing module assignments that were labeled by color and module eigengenes (ME). In addition, Pearson correlation coefficients were calculated to evaluate the correlation between ME and clinical characteristics ( 19 ). We then identified protein–protein interaction (PPI) networks using the STRING database ( http://string-db.org ).…”

Identification of Pyroptosis-Related Genes Regulating the Progression of Chronic Rhinosinusitis with Nasal Polyps

“…Differentially expressed genes (DEGs) screening employed the "limma" package and criteria as follows: correction p < 0.05 and |log2FC| > 1 [18]. Additionally, we obtained 170 pyroptosis-related gene (PRG) information from the GeneCards (https://www.genecards.org/) Website corresponding to correlation scores>0.798 [19]. We then used the "venn" package to take the intersection of the differential genes and the PRGs and showed it in a Wayne diagram.…”