In this study, we applied an integrated multi-omics approach combining structural modeling, protein–protein interaction (PPI) network analysis, and both in-silico and experimental transcriptomic validation to investigate four clinically actionable biomarkers—EGFR, ALK, KRAS, and PDCD1—central to NSCLC pathogenesis and therapy. The gene discussed is PDCD1; the disease is non-small cell lung carcinoma.