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Identification of mitophagy-related biomarkers and immune infiltration in major depressive disorder
Jing Zhang1, Shujun Xie2, Rong Xiao3
1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.
Background:
Major depressive disorder (MDD) is a life-threatening and debilitating mental health condition. Mitophagy, a form of selective autophagy that eliminates dysfunctional mitochondria, is associated with depression. However, studies on the relationship between mitophagy-related genes (MRGs) and MDD are scarce. This study aimed to identify potential mitophagy-related biomarkers for MDD and characterize the underlying molecular mechanisms.
Methods:
The gene expression profiles of 144 MDD samples and 72 normal controls were retrieved from the Gene Expression Omnibus database, and the MRGs were extracted from the GeneCards database. Consensus clustering was used to determine MDD clusters. Immune cell infiltration was evaluated using CIBERSORT. Functional enrichment analyses were performed to determine the biological significance of mitophagy-related differentially expressed genes (MR-DEGs). Weighted gene co-expression network analysis, along with a network of protein-protein interactions (PPI), was used to identify key modules and hub genes. Based on the least absolute shrinkage and selection operator analysis and univariate Cox regression analysis, a diagnostic model was constructed and evaluated using receiver operating characteristic curves and validated with training data and external validation data. We reclassified MDD into two molecular subtypes according to biomarkers and evaluated their expression levels.
Results:
In total, 315 MDD-related MR-DEGs were identified. Functional enrichment analyses revealed that MR-DEGs were mainly enriched in mitophagy-related biological processes and multiple neurodegenerative disease pathways. Two distinct clusters with diverse immune infiltration characteristics were identified in the 144 MDD samples. MATR3, ACTL6A, FUS, BIRC2, and RIPK1 have been identified as potential biomarkers of MDD. All biomarkers showed varying degrees of correlation with immune cells. In addition, two molecular subtypes with distinct mitophagy gene signatures were identified.
Conclusions:
We identified a novel five-MRG gene signature that has excellent diagnostic performance and identified an association between MRGs and the immune microenvironment in MDD.
Insights
This study identified five mitophagy-related genes as potential biomarkers for major depressive disorder (MDD), offering new diagnostic tools and insights into MDD
Area of Science:
- Molecular Biology
- Genetics
- Neuroscience
Background:
- Major depressive disorder (MDD) is a severe mental health condition.
- Mitophagy, crucial for mitochondrial quality control, is implicated in depression.
- Research on mitophagy-related genes (MRGs) in MDD is limited.
Purpose of the Study:
- To identify novel mitophagy-related gene biomarkers for MDD.
- To explore the molecular mechanisms underlying MDD related to mitophagy.
- To classify MDD into molecular subtypes based on mitophagy genes.
Main Methods:
- Analyzed gene expression data from MDD patients and controls.
- Utilized consensus clustering and immune cell infiltration analysis (CIBERSORT).
- Applied weighted gene co-expression network analysis and PPI networks to identify key genes; constructed a diagnostic model using LASSO and Cox regression.
Main Results:
- Identified 315 mitophagy-related differentially expressed genes (MR-DEGs) in MDD.
- Discovered two distinct MDD clusters with varying immune infiltration.
- Validated a five-gene signature (MATR3, ACTL6A, FUS, BIRC2, RIPK1) for MDD diagnosis with excellent performance.
Conclusions:
- A novel five-MRG gene signature demonstrates high diagnostic accuracy for MDD.
- Established a link between mitophagy-related genes and the immune microenvironment in MDD.
- Identified two MDD subtypes with distinct mitophagy gene expression profiles.
