Comprehensive analysis of ferroptosis-related genes indicates that TRIM46 is a novel biomarker and promotes the progression of ovarian cancer via modulating ferroptosis and Wnt signaling pathway.

Abstract

Ovarian cancer (OC) is a common gynecological malignant tumor with poor prognosis. One form of controlled cell death that requires iron is ferroptosis. This study utilized TCGA data analysis to identify differentially expressed genes (DEGs) related to ferroptosis in OC, revealing 2,333 up-regulated and 4,073 down-regulated genes. Venn diagrams identified 64 up-regulated and 120 down-regulated ferroptosis-related DEGs (FR-DEGs), with 15 showing a significant correlation with overall patient survival. Further analyses explored the expression, mutations, and copy number variations of these 15 FR-DEGs across various cancer types, constructing interaction networks. Molecular subtypes in OC were classified using these 15 FR-DEGs, revealing two subtypes (C1 and C2). Survival analysis identified a risk model for the C1 group based on these genes. Experimental validation highlighted TRIM46 as a key gene, with knockdown inhibiting OC cell proliferation and migration. TRIM46 was also associated with changes in ferroptosis-related markers and demonstrated a close connection with the Wnt signaling pathway, validated through Western blot experiments. Overall, the study provided a comprehensive understanding of the role of DEGs related to ferroptosis in OC, offering valuable insights into disease mechanisms and potential therapeutic targets.