Prognostic Value and Oncogenic 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). HRGs exhibited lower GAB3 and IL16 expression and worse survival outcomes. A nomogram integrating risk scores (RS) and clinical factors effectively predicted patient survival. Functional enrichment, immune landscape, and mutation analyses revealed that HRGs were more likely to immune evasion, while LRGs responded better to targeted therapies. Mutation analysis showed lower survival in patients with high-risk scores (HRS) as well as high tumor mutational burden. Immunohistochemical staining confirmed that GAB3 was upregulated in LUAD tissues. In vitro experiments demonstrated that GAB3 overexpression promoted cancer cell proliferation and migration, while siRNA-mediated knockdown of GAB3 inhibited these processes, suggesting its role as an oncogene. In conclusion, GAB3 and IL16 are key prognostic markers, providing insights into STING-related immunotherapy strategies for LUAD.