Construction of a ferroptosis-related eight gene signature for predicting the prognosis and immune infiltration of thyroid cancer

Xiaoying Ren; Huijun Du; Weilun Cheng; Yujing Wang; Yuanxin Xu; Shuang Yan; Yunan Gao

doi:10.3389/fendo.2022.997873

Construction of a ferroptosis-related eight gene signature for predicting the prognosis and immune infiltration of thyroid cancer

Front Endocrinol (Lausanne). 2022 Nov 4:13:997873. doi: 10.3389/fendo.2022.997873. eCollection 2022.

Authors

Xiaoying Ren¹, Huijun Du², Weilun Cheng³, Yujing Wang¹, Yuanxin Xu¹, Shuang Yan¹, Yunan Gao²

Affiliations

¹ Department of Endocrinology and Metabolism, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
² Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
³ Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract

Background: Thyroid cancer is the most common malignant tumor of the endocrine system. Most patients with thyroid cancer have a good prognosis, although a small proportion experience recurrence and metastasis and have a poor prognosis. Ferroptosis is a novel form of regulated cell death (RCD); previous studies have confirmed that ferroptosis was associated with thyroid cancer. The purpose of this study was to investigate the key ferroptosis-related genes in thyroid cancer and their relationship with prognosis and immune cell infiltration.

Methods: In this study, 497 thyroid cancer RNA expression datasets were downloaded from the cancer genome atlas (TCGA) cohort and a prognostic risk model for eight ferroptosis-related genes (FRGs) was constructed by Lasso-Cox regression. The prognostic value of the risk model and the correlation of prognostic features with immune scores and tumor immune cell infiltration were systematically analyzed.

Results: The prognostic risk model for eight FRGs (DPP4, TYRO3, TIMP1, CDKN2A, SNCA, NR4A1, IL-6 and FABP4) were constructed and validated in training and testing cohorts. Kaplan-Meier curve and receiver operating characteristic (ROC) curve analysis confirmed that that the ferroptosis-related eight gene signature had good predictive value for the prognosis of thyroid cancer (THCA) patients. Multivariate regression analysis further showed that the risk score of the prognostic model could be used as an independent prognostic factor for THCA patients. Functional enrichment analysis showed that DEGs in high risk and low risk groups were involved in immune-related biological processes and that there were significant differences in immune cell infiltration between the two risk groups.

Conclusion: We identified eight key genes related to ferroptosis in THCA patients. Further studies are now needed to investigate the mechanisms involved; these genes may represent clinical diagnostic and prognostic biomarkers.

Keywords: ferroptosis-related genes; immune infiltration; prognosis; thyroid cancer; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Ferroptosis* / genetics
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Kaplan-Meier Estimate
Prognosis
Thyroid Neoplasms* / diagnosis
Thyroid Neoplasms* / genetics

Substances

Biomarkers, Tumor