Accumulating studies have been conducted to identify risk genes and relevant biological mechanisms underlying major depressive disorder(MDD).In particular,transcriptomic analyses in brain regions engaged in cognitive and emotional processes,e.g.,the dorsolateral prefrontal cortex(DLPFC),have provided essential insights.Based on three independent DLPFC RNA-seq datasets of 79 MDD patients and 75 healthy controls,we performed differential expression analyses using two alternative approaches for cross-validation.We also conducted transcriptomic analyses in mice undergoing chronic variable stress(CVS)and chronic social defeat stress(CSDS).We identified 12 differentially expressed genes(DEGs)through both analytical methods in MDD patients,the majority of which were also dysregulated in stressed mice.Notably,the mRNA level of the immediate early gene FOS(Fos proto-oncogene)was significantly decreased in both MDD patients and CVS-exposed mice,and CSDS-susceptible mice exhibited a greater reduction in Fos expression compared to resilient mice.These findings suggest the potential key roles of this gene in the pathogenesis of MDD related to stress exposure.Altered transcriptomes in the DLPFC of MDD patients might be,at least partially,the result of stress exposure,supporting that stress is a primary risk factor for MDD.