Prognostic value and biological role of STING-related genes GAB3 and IL16 in lung adenocarcinoma: implications for immune evasion and treatment

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer (LC), and the stimulator of interferon genes (STING) is critical in inhibiting its progression. This study investigates the prognostic significance and molecular mechanisms of STING-related genes (STING-RGs) in LUAD. Differential expression analysis, weighted gene co-expression network analysis, as well as Cox regression (CR) identified GAB3 and IL16 as key prognostic genes. A LASSO-based risk model categorized LUAD patients into high-risk group (HRG) and low-risk group (LRG). Patients stratified into the high-risk group (HRG) displayed reduced GAB3 and IL16 expression accompanied by significantly worse survival outcomes. The nomogram combining risk score (RS) with clinical parameters provided robust prognostic discrimination. Comprehensive functional enrichment, immune landscape, and mutational analyses further revealed that the HRG exhibited marked immune-evasive characteristics, while the two risk strata showed differential susceptibilities to multiple chemotherapeutic and targeted therapies. Mutation analysis showed that patients in the Low-TMB + High-risk group had the worst survival outcomes. Western blotting analysis confirmed that GAB3 was downregulated in LUAD tissues. In vitro experiments demonstrated that GAB3 overexpression inhibited cancer cell proliferation and migration, while siRNA-mediated knockdown of GAB3 promoted these processes, suggesting its role as a tumor suppressor gene. In conclusion, GAB3 and IL16 are key prognostic markers, providing insights into STING-related immunotherapy strategies for LUAD.