Cuproptosis-related genes prediction feature and immune microenvironment in major depressive disorder

Daoyun Lei1,2, Jie Sun1,2, Jiangyan Xia1,2

  • 1Department of Anesthesiology, Zhongda Hospital Southeast University (Jiangbei), Nanjing, 210048 Jiangsu, China.

Heliyon
|August 14, 2023
PubMed
Abstract

Insights

This study reveals that dysregulated cuproptosis-related genes and activated immune responses are linked to major depressive disorder (MDD). A random forest model accurately predicts MDD risk, highlighting a potential connection between cuproptosis and depression.

Area of Science:

  • Neuroscience
  • Genetics
  • Immunology

Background:

  • Major depressive disorder (MDD) is a severe, relapsing neuropsychiatric condition with complex underlying mechanisms.
  • Cuproptosis, a recently identified form of cell death, has been implicated in various diseases, but its role in MDD remains underexplored.

Purpose of the Study:

  • To investigate the predictive value of cuproptosis-related genes for major depressive disorder (MDD).
  • To explore the association between cuproptosis-related genes and the immunological microenvironment in MDD.

Main Methods:

  • Analysis of cuproptosis regulators and immune characteristics using datasets GSE38206, GSE76826, and GSE9653.
  • Weighted gene co-expression network analysis to identify differentially expressed genes.
  • Development and validation of machine learning models (Random Forest, Generalized Linear Model, Limit Gradient Lifting) for MDD prediction.

Main Results:

  • Significant dysregulation of cuproptosis-related genes and activated immune responses were observed in MDD patients compared to healthy controls.
  • The Random Forest (RF) model, incorporating genes OSBPL8, VBP1, MTM1, ELK3, and SLC39A6, demonstrated superior discriminative performance with an AUC of 0.875.
  • The RF model showed robust predictive accuracy validated on subsequent datasets.

Conclusions:

  • A novel prediction model for MDD risk has been developed.
  • This study elucidates a potential link between cuproptosis and the pathogenesis of major depressive disorder.

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