Data Sheet 1_Acyl-CoA synthetase long-chain family member 4—A novel prognostic marker in cutaneous melanoma.docx

Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation. Acyl coenzyme A (Acyl-CoA) synthetase long-chain family member 4 (ACSL4) promotes ferroptosis by enriching cellular membranes with polyunsaturated fatty acids, yet its prognostic relevance in melanoma remains unclear. We conducted a retrospective analysis of 63 patients with melanoma to evaluate associations between ACSL4 expression and overall survival (OS), metastasis-free survival (MFS), and disease-free survival (DFS). Correlation analyses and Cox proportional hazards (CoxPH) models were used to identify prognostic factors, and immune cell infiltration was assessed in tumor samples. Higher ACSL4 expression was consistently associated with improved OS, MFS, and DFS in cutaneous melanoma. ACSL4 levels also correlated with greater immune cell infiltration within the tumor microenvironment. Notably, metastatic melanoma cases exhibited higher ACSL4 expression than non-metastatic cases; however, within cutaneous melanoma, elevated ACSL4 remained linked to more favorable survival outcomes. Together, these findings position ACSL4 as a promising prognostic biomarker in melanoma and suggest a potential connection between ferroptosis biology and antitumor immunity. While the study is retrospective and correlative, it provides a strong rationale for prospective validation and mechanistic studies to test whether modulating ACSL4-driven ferroptosis can improve clinical outcomes.