Abstract
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality, with immunotherapy proving effective only in a subset of patients, highlighting the urgent need for improved biomarkers and therapeutic targets. This study explored regulatory T cell (Treg) metabolism-related genes in NSCLC and established a seven-gene prognostic signature (TIMP1, BIRC3, G0S2, PRKCB, PDE4B, CD52, and ACP5) through multi-omics analysis. The model stratified patients into high- and low-risk groups exhibiting distinct immune profiles and drug sensitivities. Clinical validation confirmed that elevated BIRC3 and G0S2 expression correlated with poorer prognosis, while functional assays demonstrated that G0S2 inhibition suppressed tumour progression and reduced Treg infiltration in vivo. These findings position G0S2 as a promising biomarker for immunotherapy response and a potential therapeutic target, providing insights into Treg-mediated immune regulation and advancing personalized NSCLC treatment strategies.