Abstract
BACKGROUND: Major depressive disorder (MDD) and nonalcoholic fatty liver disease (NAFLD) are highly prevalent conditions that exhibit significant pathophysiological overlap, particularly in metabolic and immune pathways. OBJECTIVE: This study aims to bridge this gap by integrating transcriptomic data from publicly available repositories and advanced machine learning algorithms to identify novel biomarkers and construct a predictive model facilitates the provision of clinical psychological nursing interventions for early-stage NAFLD in MDD patients. METHOD: We systematically analyzed transcriptomic data of simple steatosis (SS), nonalcoholic steatohepatitis (NASH), and major depressive disorder (MDD) from GEO databases to construct and validate a diagnostic model. After removing batch effects, we identified differentially expressed genes (DEGs) that distinguished disease and control groups. We further applied Weighted Gene Co-expression Network Analysis (WGCNA) to identify immune-related genes in SS/NASH patients versus controls. The intersection of shared DEGs across both conditions and WGCNA-identified genes was determined and subjected to functional enrichment analysis. Immune cell infiltration levels were quantified using single-sample gene set enrichment analysis (ssGSEA). A predictive model for SS/NASH was developed by evaluating nine machine-learning algorithms with 10-fold cross-validation on the datasets. RESULTS: Fourteen genes strongly linked to both the immune system and the two conditions were identified. Immune cell infiltration profiling revealed distinct immune landscapes in patients versus healthy controls. Moreover, an eight-gene signature was developed, demonstrating superior diagnostic accuracy in both testing and training cohorts. Notably, these eight genes were found to correlate with the severity of early-stage NAFLD. CONCLUSION: This study established a predictive model for early-stage NAFLD through the integration of bioinformatics and machine learning approaches, with a focus on immune- and MDD-related genes. The eight-gene signature identified in this study represents a novel diagnostic tool for precision medicine, enabling targeted psychological nursing intervention in comorbid populations.