Abstract
INTRODUCTION: Lung cancer is a high-mortality-rate malignant tumor. Radiotherapy combined with immunotherapy shows great potential in improving patient survival. This study aims to identify gene sets associated with radiotherapy effectiveness and immune infiltration in lung adenocarcinoma (LUAD), construct a prognostic model, and preliminarily evaluate the effectiveness of the key gene TSPAN32 as a predictive diagnostic marker and therapeutic target for LUAD. METHODS: Genomic datasets from The Cancer Genome Atlas (TCGA) were analyzed to develop a 12-gene risk score model. The prognostic value of TSPAN32 was assessed, and its correlation with immune infiltration was examined. In vitro and in vivo experiments were conducted to validate the biological functions of TSPAN32 in LUAD cell lines A549 and H1299. RESULTS: The 12-gene risk score model accurately predicts prognosis and correlates with immune infiltration. TSPAN32, with high weight in the model, can independently predict prognosis and is associated with immune infiltration. TSPAN32 is significantly downregulated in LUAD cells. Its overexpression significantly inhibits the proliferation and migration of A549 and H1299 cells, enhances radiosensitivity, and may exert biological effects through the TSPAN32-PTEN signaling axis. DISCUSSION: These findings suggest that TSPAN32 could serve as a predictive biomarker for LUAD patients who may benefit from combined radiotherapy and immunotherapy, providing a theoretical basis for optimizing treatment strategies and improving patient prognosis.