Work

Pan-Cancer profiling of ferroptosis-related genes reveals prognostic biomarkers and sex-specific associations

Year: 2025

Type: article

Abstract: Aims To evaluate the association of ferroptosis-related gene expression with overall survival (OS) across multiple cancer types and explore their relationship to biological sex and radiation therapy (RT) outcomes. Methods Ferroptosis regulators were identified through a literature review and cross-referenced with the FerrDb database, yielding 55 candidate genes. Five cancers commonly treated with RT were selected. Kaplan-Meier analyses were performed to assess OS associations for each gene, with hazard ratios (HR) and p-values recorded. Segregated analysis according to biological sex were conducted on candidate genes. The analysis was repeated in a cohort of RT treated lung cancer patients. Results Across five cancers commonly treated with radiation therapy (RT), 18–35 of 55 ferroptosis-related genes were significantly associated with overall survival (OS). GLS2 and BECN1 were significantly associated with improved OS in all five cancers. SLC7A11 was significant in four cancers and generally associated with poorer OS. Sex differences in the association between these three genes and OS were detected. In RT-treated lung cancer patients (n = 65), HSPB1 , GLS2 and GPX4 were associated with improved OS, SLC7A11 with worse OS. Conclusions This study provides first evidence of sex-differences in ferroptosis-related gene expression with potential clinical relevance. This pan-cancer resource links ferroptosis-related genes to survival outcomes and highlights SLC7A11 , BECN1 , and GLS2 as high-priority candidates for future mechanistic and clinical studies. Integrating sex as a biological variable into study design and interpretation will enhance clinical relevance.

Source: Clinical and Translational Radiation Oncology

DOI: 10.1016/j.ctro.2025.101095

Authors: Max Samuel, Laure Marignol

Institution: Trinity College Dublin

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,430