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. AP1AR 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, AP1AR 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. AP1S3 and AP1S1 showed complementary roles, associated with oncogenic/inflammatory signaling and immune-metabolic programs, respectively. These findings identify AP1AR as a clinically relevant biomarker and highlight AP-1 adaptor biology as an underexplored contributor to lung adenocarcinoma progression and therapeutic stratification.