Comprehensive characterization of AP-1 adaptor complex genes in lung cancer reveals AP1AR as a novel prognostic and therapeutic biomarker

Lung cancer remains the leading cause of cancer mortality. The AP-1 adaptor complex, including AP1AR, AP1S1, AP1S2, AP1S3, AP1M1, AP1M2, AP1B1, and AP1G1, functions as a conserved hub of vesicular trafficking, selecting cargo and coordinating clathrin-mediated transport. By shaping receptor recycling, membrane composition, and signal duration, AP-1 influences core cancer phenotypes such as proliferation, migration, and therapy response. However, the family-level role of AP-1 adaptors in lung cancer is incompletely defined. We systematically profiled all eight AP-1 adaptor genes using multi-omics datasets, survival resources, pharmacogenomic panels, Human Protein Atlas data, pathway enrichment, and single-cell RNA sequencing with cell-cell communication modeling. <i>AP1AR</i> was consistently upregulated in lung adenocarcinoma and independently associated with poorer overall survival. It was linked to cell-cycle progression, DNA replication checkpoints, hypoxia, and epithelial-to-mesenchymal transition (EMT). At single cell resolution, <i>AP1AR</i> also regulate malignant epithelial and fibroblast cell types. Pseudotime analyses revealed progressive activation along proliferative and EMT axes, and CellChat modeling indicated enhanced stromal and epithelial signaling. <i>AP1S3</i> and <i>AP1S1</i> showed complementary roles, associated with oncogenic/inflammatory signaling and immune-metabolic programs, respectively. These findings identify <i>AP1AR</i> as a clinically relevant biomarker and highlight AP-1 adaptor biology as an underexplored contributor to lung adenocarcinoma progression and therapeutic stratification.