Ferroptosis-Related GPX4 and CD71 and Immune Checkpoint PD-L1 in Cutaneous Melanoma: Associations with Clinicopathologic Features and Survival Outcomes
- 1Department of Dermatology, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, Turkey
- 2Department of Pathology, Faculty of Medicine, Sivas Cumhuriyet University, 58140 Sivas, Turkey
- 3Department of Dermatology, Artvin State Hospital, 08000 Artvin, Turkey
Abstract
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.
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BibTeX
@article{guner2026ferroptosisrelated,
title = {{Ferroptosis-Related GPX4 and CD71 and Immune Checkpoint PD-L1 in Cutaneous Melanoma: Associations with Clinicopathologic Features and Survival Outcomes}},
author = {Rukiye Yasak Güner and Ramazan Oğuz Yüceer and Ahmet Turan Ünsal and Melih Akyol and Hatice Reyhan Eğilmez},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209278},
url = {https://www.mdpi.com/1422-0067/27/20/9278},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Ferroptosis-Related GPX4 and CD71 and Immune Checkpoint PD-L1 in Cutaneous Melanoma: Associations with Clinicopathologic Features and Survival Outcomes
AU - Rukiye Yasak Güner
AU - Ramazan Oğuz Yüceer
AU - Ahmet Turan Ünsal
AU - Melih Akyol
AU - Hatice Reyhan Eğilmez
PY - 2026
DA - 2026/10/01
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209278
UR - https://www.mdpi.com/1422-0067/27/20/9278
AB - 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.
SN - 1422-0067
ER -