Bioinformatic identification of genes and mechanisms related to acute respiratory distress syndrome and sepsis: A bioinformatic study

We hypothesized that acute respiratory distress syndrome (ARDS) and sepsis share hypoxia-related transcriptional signatures that reflect overlapping immunopathogenic mechanisms. This study aimed to identify shared hypoxia-related genes and associated regulatory features using bioinformatic analyses. Gene expression datasets GSE28750 and GSE76293 were analyzed separately after within-dataset normalization. Differentially expressed genes (DEGs) were defined using |logFC| > 1 and adjusted P < .05. Hypoxia-related genes were compiled from GeneCards, PubMed-curated studies, and molecular signatures database, harmonized by official gene symbols, and intersected with common DEGs from both datasets to identify hypoxia-related DEGs (HRDEGs). Gene ontology enrichment, gene set enrichment analysis, interaction network analysis, immune infiltration analysis, and protein-protein interaction analysis using STRING with a minimum interaction score of 0.400 were subsequently performed. Eleven HRDEGs were identified: capping actin protein, gelsolin-like, CKS2, CLU, FLVCR1, FUNDC1, HPSE, LCN2, MAPK14, PFKFB3, PLAC8, and TDRD9. Gene ontology enrichment suggested involvement in cellular iron ion homeostasis- and iron ion transport-related processes. Gene set enrichment analysisindicated enrichment of hypoxia- and inflammation-related pathways. Under the stricter STRING threshold (score ≥ 0.400), the protein-protein interaction network showed a limited but biologically plausible interaction pattern among the HRDEGs. Predicted miRNA, ribonucleic acid-binding protein, transcription factor, drug, and immune infiltration analyses further suggested that these genes may participate in inflammatory and immune regulatory processes relevant to ARDS and sepsis. This bioinformatic study identified shared hypoxia-associated genes in ARDS and sepsis and generated testable hypotheses regarding their possible regulatory and immunologic relevance. These findings should be interpreted as exploratory and warrant experimental validation in future studies.