Defining three ferroptosis-based molecular subtypes and developing a prognostic risk model for high-grade serous...

Area of Science:

• Oncology
• Cell Death Mechanisms
• Cancer Biomarkers

Background:

• Ferroptosis, a newly defined regulated cell death, is recognized as a potential biomarker in ovarian cancer (OV).
• The intricate mechanisms of ferroptosis within the tumor microenvironment (TME) and its clinical predictive significance in OV require further elucidation.

Purpose of the Study:

• To classify molecular subtypes of high-grade serous ovarian cancer based on ferroptosis-related genes.
• To develop and validate a ferroptosis-based prognostic model for ovarian cancer.
• To investigate the association between ferroptosis subtypes and the tumor microenvironment, immune landscape, and clinical characteristics.

Main Methods:

• Transcriptome data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases were utilized.
• Consensus clustering analysis based on ferroptosis-correlated genes from FerrDb was performed to define molecular subtypes.
• A prognostic model was constructed using 8 ferroptosis-related genes and validated across cohorts.

Main Results:

• Three distinct molecular subtypes of OV were identified, with subtype C3 showing the most favorable prognosis and C1 associated with mesenchymal features and poor outcomes.
• A robust 8-gene ferroptosis-related risk model demonstrated strong predictive performance for patient prognosis.
• High-risk patients exhibited enriched epithelial-to-mesenchymal transition (EMT) pathways, altered immune cell infiltration, and immune escape, correlating with worse outcomes.

Conclusions:

• The study successfully defined ferroptosis-related molecular subtypes in ovarian cancer, offering insights into prognosis and TME interactions.
• A validated ferroptosis-based risk model can predict clinical outcomes and potential therapeutic sensitivities in ovarian cancer patients.
• These findings provide a foundation for understanding ferroptosis in OV and developing targeted therapeutic strategies.