Signatures of 4 autophagy-related genes as diagnostic markers of MDD and their correlation with immune infiltration

Abstract

BackgroundMajor depressive disorder (MDD) is a debilitating mental illness and one of the primary causes of suicide. This study attempted to develop and validate a multigene joint signature for diagnosing MDD based on autophagy-related genes (ARGs) and to explore their biological role in MDD. MethodsWe downloaded data from the Gene Expression Omnibus (GEO) database and retrieved ARGs from the Human Autophagy Database. The limma package in R software was used to identify differentially expressed genes (DEGs). We used CIBERSORT to analyze differences in the immune microenvironment between MDD patients and controls. Finally, we examined the correlation between diagnostic markers and infiltrating immune cells to better understand the molecular immune mechanism. ResultsIn this study, we identified 20 differentially expressed ARGs in MDD compared to controls. A signature of 4 autophagy-related genes (GPR18, PDK4, NRG1 and EPHB2) was obtained. ROC analysis showed that our model has good diagnostic performance (AUC=0.779, 95% CI=0.709-0.848). Bioinformatics analysis validated that GPR18 may represent a new candidate gene for MDD. Correlation analysis revealed that GPR18 was positively correlated with regulatory T cells (Treg), CD8+ T cells, naive B cells, and memory B cells and negatively correlated with M0 macrophages and neutrophils in MDD. LimitationsThis was a second mining of previously published data sets. Independent studies are warranted to validate and improve the clinical utility of the identified signature. ConclusionsWe identified a novel four-ARG gene signature that has good diagnostic performance and identified an association between ARG genes and the immune microenvironment in MDD.