Exploring Immune-Related Ferroptosis Genes in Thyroid Cancer: A Comprehensive Analysis

<b>Background</b>: The increasing incidence and poor outcomes of recurrent thyroid cancer highlight the need for innovative therapies. Ferroptosis, a regulated cell death process linked to the tumour microenvironment (TME), offers a promising antitumour strategy. This study explored immu...

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Main Authors: Zixuan Ru, Siwei Li, Minnan Wang, Yanan Ni, Hong Qiao
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/4/903
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author Zixuan Ru
Siwei Li
Minnan Wang
Yanan Ni
Hong Qiao
author_facet Zixuan Ru
Siwei Li
Minnan Wang
Yanan Ni
Hong Qiao
author_sort Zixuan Ru
collection DOAJ
description <b>Background</b>: The increasing incidence and poor outcomes of recurrent thyroid cancer highlight the need for innovative therapies. Ferroptosis, a regulated cell death process linked to the tumour microenvironment (TME), offers a promising antitumour strategy. This study explored immune-related ferroptosis genes (IRFGs) in thyroid cancer to uncover novel therapeutic targets. <b>Methods</b>: CIBERSORTx and WGCNA were applied to data from TCGA-THCA to identify hub genes. A prognostic model composed of IRFGs was constructed using LASSO Cox regression. Pearson correlation was employed to analyse the relationships between IRFGs and immune features. Single-cell RNA sequencing (scRNA-seq) revealed gene expression in cell subsets, and qRT–PCR was used for validation. <b>Results</b>: Twelve IRFGs were identified through WGCNA, leading to the classification of thyroid cancer samples into three distinct subtypes. There were significant differences in patient outcomes among these subtypes. A prognostic risk score model was developed based on six key IRFGs (<i>ACSL5</i>, <i>HSD17B11</i>, <i>CCL5</i>, <i>NCF2</i>, <i>PSME1</i>, and <i>ACTB</i>), which were found to be closely associated with immune cell infiltration and immune responses within the TME. The prognostic risk score was identified as a risk factor for thyroid cancer outcomes (HR = 14.737, 95% CI = 1.95–111.65; <i>p</i> = 0.009). ScRNA-seq revealed the predominant expression of these genes in myeloid cells, with differential expression validated using qRT–PCR in thyroid tumour and normal tissues. <b>Conclusions</b>: This study integrates bulk and single-cell RNA sequencing data to identify IRFGs and construct a robust prognostic model, offering new therapeutic targets and improving prognostic evaluation for thyroid cancer patients.
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spelling doaj-art-03f1c391dbd44d318fd6d91fada6ccfb2025-08-20T02:24:39ZengMDPI AGBiomedicines2227-90592025-04-0113490310.3390/biomedicines13040903Exploring Immune-Related Ferroptosis Genes in Thyroid Cancer: A Comprehensive AnalysisZixuan Ru0Siwei Li1Minnan Wang2Yanan Ni3Hong Qiao4Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, ChinaDepartment of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin 150081, ChinaDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, ChinaDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, ChinaDepartment of Endocrinology and Metabolism, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China<b>Background</b>: The increasing incidence and poor outcomes of recurrent thyroid cancer highlight the need for innovative therapies. Ferroptosis, a regulated cell death process linked to the tumour microenvironment (TME), offers a promising antitumour strategy. This study explored immune-related ferroptosis genes (IRFGs) in thyroid cancer to uncover novel therapeutic targets. <b>Methods</b>: CIBERSORTx and WGCNA were applied to data from TCGA-THCA to identify hub genes. A prognostic model composed of IRFGs was constructed using LASSO Cox regression. Pearson correlation was employed to analyse the relationships between IRFGs and immune features. Single-cell RNA sequencing (scRNA-seq) revealed gene expression in cell subsets, and qRT–PCR was used for validation. <b>Results</b>: Twelve IRFGs were identified through WGCNA, leading to the classification of thyroid cancer samples into three distinct subtypes. There were significant differences in patient outcomes among these subtypes. A prognostic risk score model was developed based on six key IRFGs (<i>ACSL5</i>, <i>HSD17B11</i>, <i>CCL5</i>, <i>NCF2</i>, <i>PSME1</i>, and <i>ACTB</i>), which were found to be closely associated with immune cell infiltration and immune responses within the TME. The prognostic risk score was identified as a risk factor for thyroid cancer outcomes (HR = 14.737, 95% CI = 1.95–111.65; <i>p</i> = 0.009). ScRNA-seq revealed the predominant expression of these genes in myeloid cells, with differential expression validated using qRT–PCR in thyroid tumour and normal tissues. <b>Conclusions</b>: This study integrates bulk and single-cell RNA sequencing data to identify IRFGs and construct a robust prognostic model, offering new therapeutic targets and improving prognostic evaluation for thyroid cancer patients.https://www.mdpi.com/2227-9059/13/4/903immune-related ferroptosisthyroid cancertumour microenvironmentbiomarkerprognostic modelbioinformatics analysis
spellingShingle Zixuan Ru
Siwei Li
Minnan Wang
Yanan Ni
Hong Qiao
Exploring Immune-Related Ferroptosis Genes in Thyroid Cancer: A Comprehensive Analysis
Biomedicines
immune-related ferroptosis
thyroid cancer
tumour microenvironment
biomarker
prognostic model
bioinformatics analysis
title Exploring Immune-Related Ferroptosis Genes in Thyroid Cancer: A Comprehensive Analysis
title_full Exploring Immune-Related Ferroptosis Genes in Thyroid Cancer: A Comprehensive Analysis
title_fullStr Exploring Immune-Related Ferroptosis Genes in Thyroid Cancer: A Comprehensive Analysis
title_full_unstemmed Exploring Immune-Related Ferroptosis Genes in Thyroid Cancer: A Comprehensive Analysis
title_short Exploring Immune-Related Ferroptosis Genes in Thyroid Cancer: A Comprehensive Analysis
title_sort exploring immune related ferroptosis genes in thyroid cancer a comprehensive analysis
topic immune-related ferroptosis
thyroid cancer
tumour microenvironment
biomarker
prognostic model
bioinformatics analysis
url https://www.mdpi.com/2227-9059/13/4/903
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AT minnanwang exploringimmunerelatedferroptosisgenesinthyroidcanceracomprehensiveanalysis
AT yananni exploringimmunerelatedferroptosisgenesinthyroidcanceracomprehensiveanalysis
AT hongqiao exploringimmunerelatedferroptosisgenesinthyroidcanceracomprehensiveanalysis