Development of an Inflammation-related Gene-based Diagnostic Risk Model and Immune Infiltration Analysis in Bipolar Disorder.

IF 3.5 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current medicinal chemistry Pub Date : 2025-03-05 DOI:10.2174/0109298673355842250213103507

Jialin Gu, Kang Qian, Guolin Wu, Houxi Xu

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引用次数: 0

Abstract

Objective: This study aimed to construct a diagnostic risk model for Bipolar Disorder (BD) using inflammation-related genes (IRGs) and to explore the role of immune cell infiltration in BD pathogenesis.

Methods: BD datasets (GSE23848, GSE124326, GSE39653, and GSE46449) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the edgeR package. The intersection of DEGs and IRGs was defined as differentially expressed IRGs. A LASSO regression model was used to identify optimal biomarkers, which were then utilized to construct a diagnostic risk model. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic accuracy of the biomarkers. Internal validation was performed with GSE124326, while external validation utilized GSE23848, GSE39653, and GSE46449. The xCell module in the IOBR package was employed to assess immune cell infiltration proportions. The relationship between IRGs, the diagnostic risk model, and immune cell dynamics was further analyzed.

Results: A total of 2345 DEGs were identified in GSE124326. GO and KEGG pathway enrichment analyses indicated that inflammatory pathways are critically involved in BD pathogenesis. A total of 69 BD-related IRGs were identified. Six key IRGs (IL33, DNASE1L3, IL2RA, CD70, CLEC5A, and SLPI) were identified through LASSO regression analysis and used to develop a diagnostic risk model. Internal and external validations confirmed the robust diagnostic performance of the risk model. Immuno-infiltration analysis showed significant differences in immune cell infiltration between BD patients and healthy controls. The diagnostic risk model and four potential biomarkers (DNASE1L3, IL2RA, CD70, and SLPI) showed strong correlations with various immune cell types.

Conclusion: A diagnostic risk model for BD was constructed based on IRGs, highlighting the critical role of immune cell infiltration in BD pathogenesis.

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来源期刊

Current medicinal chemistry 医学-生化与分子生物学

CiteScore

8.60

自引率

2.40%

发文量

468

审稿时长

3 months

期刊介绍： Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.