通过转录组分析及大鼠模型验证确定的抑郁症（MDD）患者细胞趋向性相关基因特征

Abstract

Major depressive disorder (MDD) is associated with immune dysregulation, but the contribution of chemotaxis-related genes remains incompletely understood. This study aimed to identify chemotaxis-related signatures in MDD and evaluate their diagnostic relevance. Two peripheral-blood microarray datasets ( GSE76826 and GSE38206 ) were integrated after batch correction, and differentially expressed genes were intersected with the GOBP_TAXIS gene set. Hub genes were selected using random forest and SVM-RFE and evaluated by logistic regression, ROC, calibration, and decision curve analyses. Immune-cell abundance, molecular subtypes, single-nucleus expression, and in silico gene-knockout effects were further examined, followed by qRT-PCR and Western blot validation in a CUMS rat model. The integrated cohort included 21 controls and 29 MDD cases. GOBP_TAXIS activity was increased in MDD ( p < 0.001), and seven candidate genes yielded three upregulated hub genes ( CXCL2 , NRG1 , and C3AR1 ). The fixed three-gene model yielded an exploratory AUC of 0.889 in the development cohort. All three genes correlated positively with monocytes/neutrophils and negatively with T cells. Single-cell analysis revealed cell-specific enrichment, while in silico knockout simulations predicted transcriptional changes involving RORB and NTNG1 following virtual perturbation of CXCL2 and NRG1 . Animal experiments confirmed consistent upregulation at both transcriptional and translational levels. CXCL2 , NRG1 , and C3AR1 represent candidate chemotaxis-related biomarkers for MDD and are associated with distinct immune-cell abundance patterns and inflammatory signatures, warranting further functional validation.