Multi-omics integration reveals CYP2B6 as a central node in the molecular landscape of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is responsible for inducing approximately 85% of lung cancers and remains a major cause of worldwide cancer deaths. This study employed an exhaustive bioinformatics pipeline for comprehensive analysis of high-throughput RNA-sequencing data from The Cancer Genome Atlas (TCGA) to discover important molecular signatures and probable therapeutic targets in NSCLC. A total of 8,536 differential expression genes (DEGs) were identified, of which 6,241 were upregulated and 2,295 were downregulated gene expressions. Protein-protein interaction network analysis and CytoHubba-based prioritization for discovery of hub genes identified twenty core genes, out of which, CYP2B6, TEKT1, UGT1A1, UGT1A7, UGT1A8 RPTN, and AOX1 presented exceptional network centrality. Functional enrichment implicated drug metabolism, xenobiotic degradation, and chemical carcinogenesis. Mutational profiling identified frequent mutations in AOX1, RPTN, and CYP2B6. Kaplan-Meier survival analysis linked multiple expressions of hub genes to unfavorable survival. miRNA-mRNA interaction analysis uncovered conserved regulatory partnerships between miR-203 and miR-141/200a families and implicated post-transcriptional control in NSCLC pathogenesis. The drug-gene interaction analysis nominated CYP2B6 to be a key druggable target exhibitting interaction to multiple FDA drugs. The molecular docking and 500 ns molecular dynamics simulation between CYP2B6 and Pazopanib, Nilotinib, and Sorafenib validated directional and high-affinity interaction and verified RMSD, RMSF, and contact profiling. This all-encompassing study shortlists NSCLC biomarker candidates and druggable targets and gives mechanism-based understanding to disease development and drug resistance. This study gives impetus for precision medicine therapies development and suggests CYP2B6 to be a potential drug prospect.