<b>Integrative Multi-Omics Analysis Identifies a Candidate Gut Microbiota–Butyrate–JUN Regulatory Axis in Lung Adenocarcinoma</b>

We integrated two paired LUAD transcriptomic datasets, GSE40419 and GSE32863, to perform differential expression, functional enrichment, protein-protein interaction (PPI), and transcription factor (TF) activity analyses. Candidate microbial metabolites and targets were obtained from gutMGene, Similarity Ensemble Approach (SEA), and SwissTargetPrediction (STP), while Mendelian randomization (MR) was used to evaluate associations between genetically predicted gut microbial abundance and LUAD risk.

Molecular docking and a 100-ns molecular dynamics simulation were conducted to assess interactions between candidate metabolites and JUN-containing DNA-bound complexes. We identified 1,271 and 2,519 differentially expressed genes in GSE40419 and GSE32863, respectively, including 912 overlapping genes. These genes were mainly enriched in cell-cycle, immune and inflammatory, angiogenic, and tumor microenvironment-related pathways.