APOA1 as a Potential Therapeutic Target and Novel Biomarker in Lung Adenocarcinoma

Apolipoprotein A1 (APOA1), the main structural protein of high-density lipoprotein, has been implicated in cancer, but its role in lung adenocarcinoma (LUAD) remains unclear. Here, we integrate pan-cancer and LUAD-focused multi-omics with patient-serum validation, in-vitro and in-vivo functional assays, and drug-response/immune-infiltration analyses to define the role of APOA1. Public datasets (TCGA, HPA, UALCAN, cBioPortal) were used to profile expression, alterations, epigenetics, immune infiltration (CIBERSORT), and pathways (GO/KEGG/GSEA). Serum APOA1 was quantified in 60 LUAD and 30 healthy subjects. APOA1 was overexpressed in A549 and SPCA1 cells to assess proliferation, migration, and invasion; xenografts evaluated in-vivo growth. Drug-sensitivity correlations were analyzed. APOA1 is downregulated in LUAD and associates with worse survival; serum levels are reduced. Diagnostic performance was high (AUC = 0.942). APOA1 overexpression suppressed proliferation, migration, and invasion in vitro and reduced tumor volume in vivo. High APOA1 linked to complement/coagulation cascades and distinct immune infiltration. Drug sensitivity analysis revealed enhanced efficacy of agents like selumetinib in high-APOA1 tumors. This integrated, cross-layer evidence positions APOA1 as a tumor suppressor and actionable biomarker in LUAD, with implications for early detection, therapeutic stratification, and immunomodulatory strategies.