Signatures of 4 autophagy-related genes as diagnostic markers of MDD and their correlation with immune infiltration
Signatures of 4 autophagy-related genes as diagnostic markers of MDD and their correlation with immune infiltration
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4个自噬相关基因作为MDD诊断标志物的特征及其与免疫浸润的相关性
DOI：
10.1016/j.jad.2021.08.005
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发表时间：
2021-08-11
影响因子：
6.6
通讯作者：
Peng, Daihui
中科院分区：
文献类型：
--
作者：
He, Shen;Deng, Zhifang;Peng, Daihui
背景：重性抑郁障碍（MDD）是一种使人衰弱的精神疾病，也是自杀的主要原因之一。本研究试图开发和验证一种基于自噬相关基因（ARGs）的多基因联合签名用于诊断MDD，并探讨其在MDD中的生物学作用。方法：我们从基因表达综合数据库（GEO）下载数据，并从人类自噬数据库中检索ARGs。用R软件中的limma包进行差异表达基因（DEG）的鉴定。我们使用CIBERSORT分析MDD患者和对照组之间免疫微环境的差异。最后，我们研究了诊断标志物和浸润免疫细胞之间的相关性，以更好地了解分子免疫mechanism.Results：在这项研究中，我们确定了20个差异表达的ARGs在MDD相比，对照。获得了4个自噬相关基因（GPR 18、PDK 4、NRG 1和EPHB 2）的签名。ROC曲线分析表明，该模型具有良好的诊断性能（AUC=0.779，95% CI=0.709-0.848）。生物信息学分析证实GPR 18可能是MDD的一个新的候选基因。相关性分析显示，GPR 18与调节性T细胞（Treg）、CD 8 + T细胞、幼稚B细胞和记忆B细胞呈正相关，与MDD中的M0巨噬细胞和中性粒细胞呈负相关。独立的研究是必要的，以验证和提高临床效用的识别signature.Conclusions：我们确定了一种新的四ARG基因签名，具有良好的诊断性能，并确定了ARG基因和免疫微环境之间的关联MDD。
Background: Major 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.Methods: We 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.Results: In 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.Limitations: This was a second mining of previously published data sets. Independent studies are warranted to validate and improve the clinical utility of the identified signature.Conclusions: We 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.