GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE330nnn/GSE330529/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330529GEOGSEfalseTranscriptomic Profiling Identifies GPNMB as a Key Driver of Gastric Cancer AggressivenessWe aimed to define the role of GPNMB in gastric cancer (GC) progression and its underlying mechanisms. Stable GPNMB-knockdown/overexpression GC cell models were established, and transcriptomic profiling identified the cAMP signaling pathway as a key downstream effector. GPNMB silencing significantly inhibited GC cell proliferation, invasion, induced G1 arrest and apoptosis, while overexpression activated the cAMP/PKA/CREB axis to upregulate c-Myc, Cyclin D1 and EMT markers, which was reversed by the PKA inhibitor H-89. GPNMB also promoted an immunosuppressive microenvironment via IL-6 and TGF-β upregulation and accelerated xenograft tumor growth. Our findings identify GPNMB as a critical driver of GC malignancy through the cAMP/PKA/CREB axis, representing a promising therapeutic target.2026/05/17GSE330529GSM9728226GSM9728225GSM9728228GSM9728227GSM9728224GSM972822324676330529Homo sapiens