Exploring the potential role of ADRB1 as a suppressor gene and prognostic biomarker in lung adenocarcinoma: a comprehensive bioinformatics analysis

Lung adenocarcinoma (LUAD) is the most common pathological subtype of lung cancer. Sympathetic activation remodels the tumor microenvironment through β-adrenergic receptors (β-ARs) and is associated with malignant progression. Research mainly focuses on β 2 -AR, while the role of β 1 -AR (ADRB1) remains unclear. We analyzed ADRB1 expression in LUAD versus normal tissues, A549 cells and evaluated its association with survival. Cox regression assessed relationships between clinicopathological features and prognosis. We examined ADRB1 expression and pathological stage, and used gene set enrichment analysis to explore its biological functions. Associations with tumor-infiltrating immune cells and immune checkpoint genes were investigated, and potential therapeutic drugs were screened. ADRB1 expression was significantly downregulated in LUAD. ADRB1 was identified as an independent protective factor for patients with LUAD. Functional enrichment analysis showed that ADRB1 was mainly involved in chromosome segregation, cell division, mitotic cytokinesis and DNA replication in LUAD. These findings were further confirmed by in vitro experiments. Bioinformatics immune infiltration analysis revealed a significant correlation between ADRB1 expression and neutrophil infiltration abundance in lung adenocarcinoma (LUAD), suggesting that ADRB1 might be associated with the tumor immune microenvironment. In two independent LUAD cohorts, ADRB1 showed a significant negative correlation with the immune checkpoint CD276, leading to the speculation that the impact of ADRB1 on LUAD prognosis might be related to CD276 expression. Through computational screening, AZD7762 was provisionally identified as potential therapeutic agents for LUAD. In vitro assays verified that ADRB1 suppressed A549 cell proliferation and migration, supporting its function as a tumor suppressor and independent prognostic biomarker for LUAD. Transcriptomic bioinformatic analyses identified correlative links between ADRB1, neutrophil infiltration and CD276 expression. AZD7762 could serve as a potential therapeutic candidate for LUAD patients.