Prognostic significance of APOBEC1 and its role in lung squamous cell carcinoma: insights from chromatin regulator-based modeling and experimental validation.

Introduction: Chromatin regulators (CRs) are critical in cancer development, yet their prognostic value in lung squamous cell carcinoma (LUSC) remains unclear. This study aimed to develop a CR-based prognostic model and explore the role of APOBEC1 in LUSC progression.

Methods: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed. Gene Ontology and KEGG pathway enrichment were performed. Prognostic CRs were identified using univariate Cox and Lasso analyses. Drug sensitivity was assessed via the Drug Signatures Database. Key CRs were validated by PCR. APOBEC1 expression and prognosis were evaluated through pan-cancer analysis and experimentally validated in LUSC cell lines using colony formation, CCK-8, wound healing, and transwell assays.

Results: An eight-gene CR-based signature was established, achieving 5-year AUCs of 0.87, 0.92, and 0.73 in the TCGA training, validation, and GEO datasets, respectively. High-risk patients showed enrichment in cancer-related pathways, greater immune infiltration, and elevated immune checkpoint expression. They were also more sensitive to Dasatinib, Bexarotene, and Bicalutamide. APOBEC1 was overexpressed across multiple cancer types and promoted proliferation and migration in LUSC cell lines.

Conclusions: This study presents a robust CR-based survival model and highlights APOBEC1 as a potential therapeutic target in LUSC.