Cytokine-Related Genes and Inflammatory Profiles as Potential Biomarkers in Major Depressive Disorder

Cytokine-Related Genes and Inflammatory Profiles as Potential Biomarkers in Major Depressive Disorder Haein Oh1 , Na Yeong Kong1 , Sung-Won Jung1 , Hee-Cheol Kim1 , Shin Kim2 , Junho Kang3 , Hojun Lee1 1Department of Psychiatry, School of Medicine, Keimyung University, Daegu, Republic of Korea 2Department of Immunology, School of Medicine, Keimyung University, Daegu, Republic of Korea 3Department of Research, Keimyung University Dongsan Medical Center, Daegu, Republic of Korea Correspondence: Junho Kang ,Tel: +82-53-258-4881, Email: junho6399@dsmc.or.kr Correspondence: Hojun Lee ,Tel: +82-53-258-4881, Fax: +82-53-258-4882, Email: hojunlee@kmu.kr Received: January 7, 2025 Revised: April 7, 2025 Accepted: May 19, 2025 Published online: July 31, 2025 Abstract Objective Based on the neuroimmunological hypothesis of major depressive disorder (MDD), we analyzed the existing research to identify cytokine-related genes associated with MDD. Furthermore, we examined the cytokine alterations in patients with MDD as potential biomarkers for diagnosis and monitoring. Methods Differentially expressed genes (DEGs) related to MDD were identified using the GEO2R tool on public datasets, followed by functional enrichment analyses with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. Protein-protein interaction (PPI) networks were constructed using Cytoscape to identify hub genes. Finally, blood samples from 20 patients with MDD and 10 healthy controls were analyzed using the Olink® Target 96 Inflammation panel with proximity extension assay (PEA) technology to identify potential protein biomarkers. Results Two GEO datasets related to MDD were analyzed to identify 66 common DEGs. Following the PPI analysis, 46 genes were identified. Functional enrichment analysis revealed that these genes were closely related to immune-related pathways. Subsequent blood sample analysis of patients with MDD and healthy controls confirmed that 18 cytokines related to 46 DEGs were significantly upregulated. Among the identified cytokines, oncostatin M (OSM) showed the highest receiver operating characteristic (ROC) performance (area under the curve [AUC]=0.96), followed by hepatocyte growth factor (HGF) (AUC=0.95), cluster of differentiation 6 (CD6) (AUC=0.90), and tumor necrosis factor superfamily 14 (TNFSF14) (AUC=0.90). Conclusion Our study confirms that neuroinflammation is an important pathophysiological aspect of MDD and that several related cytokines, such as OSM, HGF, CD6, and TNFSF14, may be potential biomarkers of MDD.