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

• Published in: Frontiers in medicine 2021-04, Vol.8, p.637743-637743
• Main Authors: Ge, Mingqin, Niu, Jie, Hu, Ping, Tong, Aihua, Dai, Yan, Xu, Fangjiang, Li, Fuyuan
• Format: Article
• Language: English
• Subjects: ferroptosis; gene signature; immune microenvironment; Medicine; prognosis; thyroid cancer
• ISSN: 2296-858X; 2296-858X
• DOI: 10.3389/fmed.2021.637743

This study aimed to construct a prognostic ferroptosis-related signature for thyroid cancer and probe into the association with tumor immune microenvironment. Based on the expression profiles of ferroptosis-related genes, a LASSO cox regression model was established for thyroid cancer. Kaplan-Meier survival analysis was presented between high and low risk groups. The predictive performance was assessed by ROC. The predictive independency was validated multivariate cox regression analysis and stratified analysis. A nomogram was established and verified by calibration curves. The enriched signaling pathways were predicted GSEA. The association between the signature and immune cell infiltration was analyzed by CIBERSORT. The ferroptosis-related genes were validated in thyroid cancer tissues by immunohistochemistry and RT-qPCR. A ferroptosis-related eight gene model was established for predicting the prognosis of thyroid cancer. Patients with high risk score indicated a poorer prognosis than those with low risk score ( = 1.186e-03). The AUCs for 1-, 2-, and 3-year survival were 0.887, 0.890, and 0.840, respectively. Following adjusting other prognostic factors, the model could independently predict the prognosis ( = 0.015, HR: 1.870, 95%CI: 1.132-3.090). A nomogram combining the signature and age was constructed. The nomogram-predicted probability of 1-, 3-, and 5-year survival approached the actual survival time. Several ferroptosis-related pathways were enriched in the high-risk group. The signature was distinctly associated with the immune cell infiltration. After validation, the eight genes were abnormally expressed between thyroid cancer and control tissues. Our findings established a prognostic ferroptosis-related signature that was associated with the immune microenvironment for thyroid cancer.