Screening key genes related to neuropathic pain-induced depression through an integrative bioinformatics analysis

Ann Transl Med. 2022 Dec;10(24):1348. doi: 10.21037/atm-22-5820.

Abstract

Background: Neuropathic pain (NP) is often accompanied by sleep disorders, anxiety, depression and other complications, and the pathogenesis is still unclear. Some drugs can relieve patients' pain, but the overall effect is not good. We screened for the key genes related to NP-induced depression based on bioinformatics.

Methods: The dataset of GSE92718 was obtained from the Gene Expression Omnibus database, data mining was conducted based on R language, the genes modules were screened by weighted correlation network analysis, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed, a protein-protein interaction (PPI) network was constructed in the STRING database, and hub genes were screened according to degree value.

Results: Seven modules were obtained and built to identify the relationships between the NP-induced depression and the modules, weighted gene co-expression network analysis (WGCNA) was used to identify gene modules closely related to the experimental group. The GO annotations of depression-related genes mainly enriched in protein polyubiquitination, regulation of chromosome organization, mitochondrial matrix, mitochondrial protein-containing complex, etc. KEGG enrichment analysis results were: Alzheimer's disease, Huntington's disease, ribosome, thermogenesis, prion disease, non-alcoholic fatty liver disease, diabetic cardiomyopathy, oxidative phosphorylation, retrograde endocannabinoid signaling, 2-oxocarboxylic acid metabolism. PPI network analysis showed that Polr2f, Rps13, Mrpl2, Mrpl40, Mrpl34, and Ndufs8 were more highly expressed in NP-induced depression. Functional analysis of key genes showed that these genes were related to mitochondrial translation termination, respiratory chain complex I, mitochondrial, mRNA Splicing (minor pathway), and of rRNA processing in the nucleolus and cytosol (major pathway).

Conclusions: The key genes of depression induced by NP are Polr2f, Rps13, Mrpl2, Mrpl40, Mrpl34, and Ndufs8.

Keywords: Bioinformatics analysis; depression; hub genes; neuropathic pain (NP).