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一种新型的 4 种免疫相关基因作为诊断标志物,与重度抑郁症中的免疫浸润相关。

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

机构信息

Department of Pathology, Gannan Medical University Pingxiang Hospital, Pingxiang, China.

出版信息

BMC Immunol. 2022 Feb 13;23(1):6. doi: 10.1186/s12865-022-00479-3.

Abstract

BACKGROUND

Immune 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.

METHODS

We 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.

RESULTS

203 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.

CONCLUSIONS

We 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.

摘要

背景

免疫反应与重度抑郁症(MDD)的病理生理学普遍相关。然而,关于免疫相关基因(IRGs)与 MDD 免疫浸润之间关系的研究仍然很少。

方法

我们从 2 个队列中提取了 148 名 MDD 患者的表达数据,并使用 R 软件中的 limma 包系统地描述了差异表达的 IRGs。然后,使用 LASSO 和多元逻辑回归分析来识别最强大的 IRGs。接下来,我们分析了 IRGs 与 MDD 免疫浸润之间的关系。最后,使用 GSE76826 验证了 IRGs 作为 MDD 的诊断标志物。

结果

在 MDD 中鉴定出 203 个不同的 IRGs(P<0.05)。GSEA 显示,不同的 IRGs 更有可能富集在免疫特异性途径中。然后,我们使用 LASSO 成功建立了一个基于 9 个 IRGs 的 MDD 预测模型。接下来,通过多元逻辑回归分析获得了 4 个 IRGs,CD1C、SPP1、CD3D、CAMKK2 和 IRGs 模型的 AUC 分别为 0.733、0.767、0.816、0.800 和 0.861,表明它们具有良好的诊断性能。此外,MDD 组的 T 细胞 CD8、T 细胞 γδ、M0 巨噬细胞和 NK 细胞静息比例低于健康对照组,表明 MDD 组的免疫系统受损。同时,CD3D 被验证为 MDD 的可靠标志物,与 T 细胞 CD8 呈正相关。GSEA 显示,高表达的 CD3D 更有可能富集在免疫特异性途径中,而低表达的 CD3D 更有可能富集在葡萄糖代谢特异性途径中。

结论

我们应用生物信息学方法表明,4 个 IRGs 可以作为诊断标志物,为探索 MDD 的发病机制提供了新的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb0f/8842937/dcea6a0c9414/12865_2022_479_Fig1_HTML.jpg

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