AUTHOR=Gou Zi-han , Su Nan , Li Xiao-chuan , Ren Da-peng , Ren Shan-shan , Wang Lin , Wang Yao 

TITLE=Integrated transcriptomic and immune profiling reveals crucial molecular pathways and hub genes associated with postoperative delirium in elderly patients

JOURNAL=Frontiers in Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2025.1580355

DOI=10.3389/fmed.2025.1580355

ISSN=2296-858X

ABSTRACT=BackgroundPostoperative delirium (POD) manifests as severe mental disorientation, often experienced by elderly patients undergoing surgery, significantly hindering recovery and deteriorating the quality of life. Despite numerous clinical studies, the molecular mechanisms behind POD in elderly patients are still not well understood, requiring further investigation to identify potential biomarkers and therapeutic targets.MethodsThis study amalgamates Gene Set Variation Analysis (GSVA), Weighted Gene Co-expression Network Analysis (WGCNA), differential expression analysis, and immune infiltration assessments to identify molecular pathways and hub genes linked to the initiation of POD in the elderly. Gene expression data were sourced from the GSE163943 dataset in the Gene Expression Omnibus (GEO) database. A total of 18,894 protein-coding genes were extracted for analysis.ResultsWe constructed a gene co-expression network using WGCNA and performed GSVA to investigate the link between POD and different types of cell death. The results indicated that POD is positively associated with pyroptosis and parthanatos, while negatively correlated with oxidative stress and disulfidptosis. Differential expression analysis revealed 145 differentially expressed genes (DEGs), including 83 downregulated and 62 upregulated genes. Analysis of functional enrichment revealed that DEGs were enriched in activities like neuron projection development, axonogenesis, and synapse organization, with KEGG pathway analysis identifying neuroactive ligand-receptor interaction and neurodegeneration pathways. Gene Set Enrichment Analysis (GSEA) further revealed the upregulation of the apoptosis pathway and the downregulation of neuroactive ligand-receptor interaction. Protein–protein interaction (PPI) network analysis identified 10 hub genes, including COL18A1, CD63, and LTF. Immune infiltration analysis indicated that the occurrence of POD is strongly associated with immune cell activation, particularly in T cells and macrophages.ConclusionOverall, this research primarily examines the intricate interplay between cell death processes and alterations in the immune microenvironment throughout the development of geriatric POD, pinpointing essential genes that provide vital theoretical support for further studies on geriatric POD. However, this discovery is only an initial one derived from analyzing the datasets. Upcoming research ought to evaluate and scrutinize additional datasets and conduct essential experiments to guarantee the precision and widespread relevance of the analytical findings.