Identification and Validation of a Prognostic Signature for Thyroid Cancer Based on Ferroptosis-Related Genes.

[BACKGROUND] Thyroid cancer is the most common endocrine malignancy. Most PTC patients have a good prognosis; however, there are 5-20% of PTC patients with extra-thyroidal invasion, vascular invasion, or distant metastasis who have relatively poor prognoses. The aim of this study is to find new and feasible molecular pathological markers and therapeutic targets for early identification and appropriate management.

[METHODS] The GEO and TCGA databases were used to gather gene expression data and clinical outcomes. Based on gene expression and clinical parameters, we developed a ferroptosis-related gene-based prognostic model and a nomogram. CCK-8, wound-healing, and transwell assays were conducted to explore the proliferation, migration, and invasion abilities of thyroid cancer cells.

[RESULTS] We found 75 genes associated with ferroptosis that were differentially expressed between normal thyroid tissue and thyroid cancer tissues. The prognostic values of the 75 ferroptosis-related gene expressions were evaluated using the TCGA-THCA dataset, and five (AKR1C3, BID, FBXW7, GPX4, and MAP3K5) of them were of significance. Following that, we chose AKR1C3 as the subject for further investigation. By combining gene expression and clinical parameters, we developed a ferroptosis-related gene-based prognostic model with an area under the curve (AUC) of 0.816, and the nomogram also achieved good predictive efficacy for the three-year survival rate of thyroid cancer patients. Knocking down AKR1C3 enhances thyroid cancer cell proliferation, invasion, and migration abilities.

[CONCLUSIONS] A ferroptosis-related gene-based prognostic model was constructed that provided unique insights into THCA prognosis prediction. In addition, AKR1C3 was found to be a progression promoter in thyroid cancer cell lines.