Identification of endoplasmic reticulum stress-related biomarkers of diabetes nephropathy based on bioinformatics and machine learning

Abstract

Background: Diabetes nephropathy (DN) is a growing public health concern worldwide. Renal dysfunction impairment in DN is intimately linked to ER stress and its related signaling pathways. Nonetheless, the underlying mechanism and biomarkers for this function of ER stress in the DN remain unknown. Methods: Microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database, and ER stress-related genes (ERSRGs) were downloaded from the MSigDB and GeneCards database. We identified hub ERSRGs for DN progression by intersecting ERSRGs with differentially expressed genes and significant genes in WGCNA, followed by a functional analysis. After analyzing hub ERSRGs with three machine learning techniques and taking the intersection, we did external validation as well as developed a DN diagnostic model based on the characteristic genes. Immune infiltration was performed using CIBERSORT. Moreover, patients with DN were then categorized using a consensus clustering approach. Eventually, the candidate ERSRGs-specific small-molecule compounds were defined by CMap. Results: Several biological pathways driving pathological injury of DN and disordered levels of immune infiltration were revealed in the DN microarray datasets and strongly related to deregulated ERSRGs by bioinformatics multi-chip integration. Moreover, CDKN1B, EGR1, FKBP5, GDF15, and MARCKS were identified as ER stress signature genes associated with DN by machine learning algorithms, demonstrating their potential as DN biomarkers. Conclusions: Our research sheds fresh light on the function of ER stress in DN pathophysiology and the development of early diagnostic and ER stress-related treatment targets in patients with DN.

β-Arrestin-2 enhances ER stress-induced glomerular endothelial cells injury through ATF6 in diabetic nephropathy

“…Endoplasmic reticulum (ER) stress is one of the major cellular mechanisms involved in kidney injury in DN 33 . Numerous studies have demonstrated that the dysfunction of ER stress is associated with onset and progression of DN, ER stress inhibitors decreased ER stress and halted the progression of DN 34,35 . However, some studies demonstrated that activated ER stress had a protective role on DN which re ected the bidirectional control of ER stress in DN 36 .…”

SKP alleviates the ferroptosis in diabetic kidney disease through suppression of HIF-1α/HO-1 pathway based on network pharmacology analysis and experimental validation

“…Last several years, the global prevalence of Diabetes mellitus (DM) has been on the rise, paralleled by a gradual increase in diabetes-related diabetic kidney disease (DKD) [ 1 ]. DKD, a severe microvascular complication of DM, presents clinically with elevated blood glucose, proteinuria and diminished glomerular filtration rate [ 2 ].…”