A Ferroptosis-Related Signature Robustly Predicts Clinical Outcomes and Associates With Immune Microenvironment for...

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Thyroid cancer prognosis remains challenging.
• Ferroptosis, a regulated cell death, plays a role in cancer.
• Understanding the tumor immune microenvironment is crucial for treatment.

Purpose of the Study:

• To develop a prognostic signature based on ferroptosis-related genes for thyroid cancer.
• To investigate the association between this signature and the tumor immune microenvironment.
• To validate the signature's predictive power and clinical utility.

Main Methods:

• Ferroptosis-related gene expression data was used to build a LASSO Cox regression model.
• Kaplan-Meier survival analysis, ROC curves, and multivariate Cox regression were employed for validation.
• Gene Set Enrichment Analysis (GSEA) and CIBERSORT were used to analyze pathways and immune cell infiltration.
• Immunohistochemistry and RT-qPCR validated key gene expression in thyroid cancer tissues.

Main Results:

• An eight-gene ferroptosis-related signature was established, significantly predicting thyroid cancer prognosis.
• High-risk patients exhibited poorer survival (p=1.186e-03), with AUCs for 1-, 2-, and 3-year survival at 0.887, 0.890, and 0.840.
• The signature independently predicted prognosis (p=0.015) and was integrated into a nomogram with age.
• Significant associations were found between the signature and immune cell infiltration, with validated abnormal gene expression.

Conclusions:

• A novel prognostic signature based on ferroptosis-related genes was successfully developed for thyroid cancer.
• This signature is significantly associated with the tumor immune microenvironment, offering potential therapeutic targets.
• The findings provide a valuable tool for predicting thyroid cancer prognosis and understanding its immunobiology.