Molecular mechanism and diagnostic marker investigation of endoplasmic reticulum stress on periodontitis

Abstract

Abstract Purpose The aim of this study was to reveal the biological function of endoplasmic reticulum stress (ERS)-related genes (ERSGs) in periodontitis, and provide potential ERS diagnostic markers for clinical therapy of periodontitis. Methods The differentially expressed ERSGs (DE-ERSGs) were reveled based on periodontitis-related microarray dataset in Gene Expression Omnibus (GEO) database and 295 ERS in previous study, followed by a protein–protein interaction network construction. Then, the subtypes of periodontitis were explored, followed by validation with immune cell infiltration and gene set enrichment. Two machine learning algorithms were used to reveal potential ERS diagnostic markers of periodontitis. The diagnostic effect, target drug and immune correlation of these markers were further evaluated. Finally, a microRNA(miRNA)-gene interaction network was constructed. Results A total of 34 DE-ERSGs were revealed between periodontitis samples and control, followed by two subtypes investigated. There was a significant difference of ERS score, immune infiltration and Hallmark enrichment between two subtypes. Then, totally 7 ERS diagnostic markers including FCGR2B, XBP1, EDEM2, ATP2A3, ERLEC1, HYOU1 and YOD1 were explored, and the v the time-dependent ROC analysis showed a reliable result. In addition, a drug-gene network was constructed with 4 up-regulated ERS diagnostic markers and 24 drugs. Finally, based on 32 interactions, 5 diagnostic markers and 20 miRNAs, a miRNA-target network was constructed. Conclusions Up-regulated miR-671-5p might take part in the progression of periodontitis via stimulating the expression of ATP2A3. ERSGs including XBP1 and FCGR2B might be novel diagnostic marker for periodontitis.