Ferroptosis-Related GPX4 and CD71 and Immune Checkpoint PD-L1 in Cutaneous Melanoma: Associations with Clinicopathologic Features and Survival Outcomes

Ferroptosis-related pathways and immune checkpoint signaling may contribute to melanoma progression, but their clinicopathologic and prognostic interplay remains incompletely characterized. To investigate GPX4, CD71, and PD-L1 expression in primary cutaneous melanoma and evaluate their associations with clinicopathologic features and survival outcomes. This retrospective single-center cohort included 44 patients with primary cutaneous melanoma. PD-L1, GPX4, and CD71 expressions were assessed immunohistochemically. Associations with clinicopathologic parameters were analyzed, and overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan–Meier and Cox regression analyses. PD-L1, GPX4, and CD71 positivity was were observed in 25.0%, 38.6%, and 36.4% of tumors, respectively. PD-L1 expression was associated with Breslow thickness (p = 0.004), whereas CD71 expression was associated with perineural invasion, Clark level, and disease stage (p = 0.019, p = 0.034, and p = 0.045, respectively). GPX4-positive tumors showed significantly shorter OS (40 vs. 103 months; p = 0.003) and DFS (42 vs. 86 months; p = 0.009). Triple-positive tumors (PD-L1+/GPX4+/CD71+) demonstrated significantly shorter OS and DFS than triple-negative tumors (p = 0.035 and p = 0.040, respectively). In multivariable analysis, GPX4 positivity remained independently associated with poorer OS. GPX4 expression was associated with adverse survival outcomes in cutaneous melanoma, while combined GPX4, CD71, and PD-L1 expression identified a subgroup with particularly unfavorable outcomes. These findings support further investigation of ferroptosis-related markers alongside immune checkpoint pathways as candidate prognostic biomarkers in melanoma.