Lung adenocarcinoma (LUAD) represents the predominant subtype of non-small cell lung cancer, with limited survival improvements despite advances in targeted therapies, underscoring the need for novel biomarkers and therapeutic targets. Apolipoprotein A1 (APOA1), a major component of high-density lipoprotein involved in cholesterol transport, has been linked to tumorigenesis. However, its role in LUAD remains unclear. Multi-omics analyses were conducted using TCGA, HPA, UALCAN, cBioPortal, and other databases to assess APOA1 expression, mutations, epigenetic modifications, prognostic correlations, immune infiltration via CIBERSORT, and pathway enrichment through GO, KEGG, and GSEA. We analyzed TCGA transcriptomic data to assess APOA1 expression in pan-cancer contexts, focusing on LUAD. Serum APOA1 levels were quantified by ELISA in 60 LUAD patients and 30 healthy controls. In vitro experiments involved APOA1 overexpression in A549 and SPCA1 cell lines, evaluated by Western blot, CCK-8 proliferation assay, and Transwell assays. In vivo tumor growth was assessed in nude mouse xenografts. APOA family genes predominantly exhibit amplifications and mutations in pan-cancer. APOA1 was significantly downregulated in LUAD tissues and serum, correlating with poor overall survival (AUC=0.942 for diagnostic accuracy). APOA1 modulates immunity and pathways like complement cascades. Overexpression inhibited cell proliferation, migration, and invasion in vitro, and reduced xenograft tumor volumes in vivo. Drug sensitivity analysis revealed enhanced efficacy of agents like selumetinib in high-APOA1. These findings position APOA1 as a tumor suppressor and prognostic biomarker in LUAD, offering potential for targeted therapies to improve patient outcomes.
Sun et al. (Sat,) studied this question.