A novel 4 immune-related genes as diagnostic markers and correlated with immune infiltrates in major depressive disorder

Linna Ning,Huiming Li,Dandong Deng,Yan Xu,Zhou Yang,Wenrui Jiang,Lixia Guo,Jie Chen,Fanghua Xu,Zhaopeng Hu

doi:10.1186/s12865-022-00479-3

Abstract

BackgroundImmune response is prevalently related with major depressive disorder (MDD) pathophysiology. However, the study on the relationship between immune-related genes (IRGs) and immune infiltrates of MDD remains scarce.MethodsWe extracted expression data of 148 MDD patients from 2 cohorts, and systematically characterized differentially expressed IRGs by using limma package in R software. Then, the LASSO and multivariate logistic regression analysis was used to identify the most powerful IRGs. Next, we analyzed the relationship between IRGs and immune infiltrates of MDD. Finally, GSE76826 was used to to verificate of IRGs as a diagnostic markers in MDD.Results203 different IRGs s in MDD has been identified (P < 0.05). GSEA revealed that the different IRGs was more likely to be enriched in immune-specific pathways. Then, a 9 IRGs was successfully established to predict MDD based on LASSO. Next, 4 IRGs was obtained by multivariate logistic regression analysis, and AUC for CD1C, SPP1, CD3D, CAMKK2, and IRGs model was 0.733, 0.767, 0.816, 0.800, and 0.861, suggesting that they have a good diagnostic performance. Furthermore, the proportion of T cells CD8, T cells γδ, macrophages M0, and NK cells resting in MDD group was lower than that in the healthy controls, suggesting that the immune system in MDD group is impaired. Simultaneously, CD3D was validated a reliable marker in MDD, and was positively correlated with T cells CD8. GSEA revealed high expression CD3D was more likely to be enriched in immune-specific pathways, and low expression CD3D was more likely to be enriched in glucose metabolism metabolism-specific pathways.ConclusionsWe applied bioinformatics approaches to suggest that a 4 IRGs could serve as diagnostic markers to provide a novel direction to explore the pathogenesis of MDD.

Highlights

Major Depression Disorder (MDD) is an affective mental disorder syndrome with low mood, lack of interest and loss of fun as the main symptoms, accompanied by anxiety, cognitive impairment, psycho-motor disorder, and even suicide tendency [1,2,3]
There was no significant difference in CD1C (P = 0.77), SPP1 (P = 0.66), and CAMKK2 (P = 0.29) (Fig. 4A–D). These results support that CD3D was validated a reliable marker in major depressive disorder (MDD)
By detecting immune infiltrates between the MDD group and healthy controls, we found that the proportion of T cells CD8, T cells γδ, macrophages M0, and NK cells resting in MDD group was lower than that in the healthy controls, suggesting that the immune system in MDD group is impaired

Summary

Introduction

Major Depression Disorder (MDD) is an affective mental disorder syndrome with low mood, lack of interest and loss of fun as the main symptoms, accompanied by anxiety, cognitive impairment, psycho-motor disorder, and even suicide tendency [1,2,3]. Clinical diagnosis is mainly based on symptom description, mental state examination and clinical behavior observation of patients, lacking objective diagnostic indicators, which increases the misdiagnosis rate to a large extent [6]. Since modern drugs with selective serotonin reuptake inhibitor (SSRI), based on the monoamine neurotransmitter hypothesis, have shown only 50–60% efficacy in a large number of clinical studies [7, 8]. All of these problems hinder the diagnosis and treatment of MDD. Immune response is prevalently related with major depressive disorder (MDD) pathophysiology. The study on the relationship between immune-related genes (IRGs) and immune infiltrates of MDD remains scarce

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