甲状腺未分化癌相关铁死亡关键基因筛选及免疫浸润分析

徐润; 李金朋; 陈伟贞; 吴高松

doi:10.14188/j.1671-8852.2024.0182

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甲状腺未分化癌相关铁死亡关键基因筛选及免疫浸润分析

基础及临床医学研究 | 更新时间：2026-11-05

- 甲状腺未分化癌相关铁死亡关键基因筛选及免疫浸润分析
- Screening of hub iron death⁃related genes in anaplastic thyroid carcinoma and immune infiltration analysis
- 武汉大学学报（医学版） 2025年46卷第4期页码：493-499
- 作者机构：
  
  武汉大学中南医院甲状腺乳腺外科湖北武汉 430071
- 作者简介：
  
  徐润，男，1998—，医学硕士生，主要从事甲状腺乳腺肿瘤研究，E⁃mail:xurunwhu@163.com
  吴高松，男，1966—，医学博士，主任医师，博士生导师，主要从事甲状腺乳腺肿瘤研究，E⁃mail:Wugaosongtj@163.com
- 基金信息：
  
  湖北省自然科学基金面上项目(2021CFB427);武汉大学中南医院转化医学与交叉学科研究联合基金项目(ZNJC202304)
- DOI：10.14188/j.1671-8852.2024.0182
  中图分类号： R736.1
- 纸质出版：2025-04-25
- 稿件说明：
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徐润,李金朋,陈伟贞等.甲状腺未分化癌相关铁死亡关键基因筛选及免疫浸润分析[J].武汉大学学报（医学版）,2025,46(04):493-499.

XU Run,LI Jinpeng,CHEN Weizhen,et al.Screening of hub iron death⁃related genes in anaplastic thyroid carcinoma and immune infiltration analysis[J].Medical Journal of Wuhan University,2025,46(04):493-499.
徐润,李金朋,陈伟贞等.甲状腺未分化癌相关铁死亡关键基因筛选及免疫浸润分析[J].武汉大学学报（医学版）,2025,46(04):493-499. DOI： 10.14188/j.1671-8852.2024.0182.

XU Run,LI Jinpeng,CHEN Weizhen,et al.Screening of hub iron death⁃related genes in anaplastic thyroid carcinoma and immune infiltration analysis[J].Medical Journal of Wuhan University,2025,46(04):493-499. DOI： 10.14188/j.1671-8852.2024.0182.

摘要

目的

分析甲状腺未分化癌（ATC）组织中铁死亡相关基因的表达，构建PPI网络并对ATC中与铁死亡通路相关的重要基因进行关键基因验证和免疫浸润检测。

方法

从GEO数据库中获取数据，归一化后筛选差异基因进行富集分析，与数据库取交集后，通过蛋白互作（PPI）网络及MCC评分确定得到铁死亡关键基因，评估诊断价值。使用CIBERSORT分析评估样本的免疫浸润情况。

结果

确定8个铁死亡基因与ATC密切相关，并具备潜在诊断作用。GO和KEGG分析得出了可能与肿瘤相关的细胞途径和生物成分。此外，通过免疫浸润分析确定了ATC样本中免疫细胞的组成和与铁死亡基因的相关性，发现铁死亡关键基因影响免疫细胞表达从而导致肿瘤进展，揭示调节性T细胞⁃CD4记忆激活T细胞通路在ATC中的潜在作用。

结论

本研究确定了8个铁死亡关键基因为ATC诊断的生物标志物和潜在治疗靶点，同时还发现可能通过影响调节性T细胞⁃CD4记忆激活T细胞导致免疫环境紊乱的通路，为进一步探讨ATC的发病机制提供理论基础。

Abstract

Objective

To analyze the expression of iron death⁃related genes in anaplastic thyroid carcinoma (ATC) tissue， construct a protein⁃protein interaction (PPI) network

and detect hub gene and immune infiltration related to the iron death pathway in ATC.

Methods

Data were obtained from the GEO database

normalized

and screened for differential genes for enrichment analysis

and after taking the intersection with the database

the hub genes related to iron death were determined to be obtained through the protein⁃protein interaction （PPI) network and the MCC score to assess the diagnostic value. Additionally

CIBERSORT analysis was used to assess the immune infiltration status of samples.

Results

Eight iron death genes were identified to be closely associated with ATC and potentially serve as diagnostic markers. GO and KEGG analyses yielded cellular pathways and biological components that may be relevant to tumors. Furthermore

immune infiltration analysis determined the composition of immune cells in ATC samples and their correlation with iron death genes

revealing that hub iron death genes influence immune cell expression

thereby contributing to tumor progression. It unveiled the potential role of the regulatory T cell⁃CD4 memory⁃activated T cell pathway in ATC.

Conclusion

This study identified eight hub iron death genes as diagnostic biomarkers and potential therapeutic targets for ATC. Additionally

it discovered pathways possibly causing immune environment disturbance through the regulation of regulatory T cell⁃CD4 memory activated T cells

laying the foundation for further exploration of the pathogenesis of ATC.

关键词

Keywords

references

SIEGEL R L , MILLER K D , WAGLE N S , et al . Cancer statistics, 2023 [J ] . CA Cancer J Clin , 2023 , 73 ( 1 ): 17 ⁃ 48 .

ZHENG R S , ZHANG S W , ZENG H M , et al . Cancer incidence and mortality in China, 2016 [J ] . J Natl Cancer Cent , 2022 , 2 ( 1 ): 1 ⁃ 9 .

JANNIN A , ESCANDE A , AL GHUZLAN A , et al . Anaplastic thyroid carcinoma: An update [J ] . Cancers , 2022 , 14 ( 4 ): 1061 .

MANIAKAS A , DADU R , BUSAIDY N L , et al . Evaluation of overall survival in patients with anaplastic thyroid carcinoma, 2000⁃2019 [J ] . JAMA Oncol , 2020 , 6 ( 9 ): 1397 ⁃ 1404 .

JIANG X J , STOCKWELL B R , CONRAD M . Ferroptosis: Mechanisms, biology and role in disease [J ] . Nat Rev Mol Cell Biol , 2021 , 22 ( 4 ): 266 ⁃ 282 .

CHEN X , KANG R , KROEMER G , et al . Broadening horizons: The role of ferroptosis in cancer [J ] . Nat Rev Clin Oncol , 2021 , 18 ( 5 ): 280 ⁃ 296 .

TANG D L , CHEN X , KANG R , et al . Ferroptosis: Molecular mechanisms and health implications [J ] . Cell Res , 2021 , 31 ( 2 ): 107 ⁃ 125 .

D'APRILE S , DENARO S , PAVONE A M , et al . Anaplastic thyroid cancer cells reduce CD71 levels to increase iron overload tolerance [J ] . J Transl Med , 2023 , 21 ( 1 ): 780 .

WU J J , LIANG J Y , LIU R Q , et al . Autophagic blockade potentiates anlotinib⁃mediated ferroptosis in anaplastic thyroid cancer [J ] . Endocr Relat Cancer , 2023 , 30 ( 9 ): e230036 .

IYER PC , DADU R , FERRAROTTO R , et al . Real⁃world experience with targeted therapy for the treatment of anaplastic thyroid carcinoma [J ] . Thyroid , 2018 , 28 ( 1 ): 79 ⁃ 87 .

LI J , CAO F , YIN H L , et al . Ferroptosis: Past, present and future [J ] . Cell Death Dis , 2020 , 11 ( 2 ): 88 .

LEI G , ZHUANG L , GAN B Y . Targeting ferroptosis as a vulnerability in cancer [J ] . Nat Rev Cancer , 2022 , 22 ( 7 ): 381 ⁃ 396 .

LI M Y , JIN S F , ZHANG Z Y , et al . Interleukin⁃6 facilitates tumor progression by inducing ferroptosis resistance in head and neck squamous cell carcinoma [J ] . Cancer Lett , 2022 , 527 : 28 ⁃ 40 .

DIXON S J , LEMBERG K M , LAMPRECHT M R , et al . Ferroptosis: An iron⁃dependent form of nonapoptotic cell death [J ] . Cell , 2012 , 149 ( 5 ): 1060 ⁃ 1072 .

ZHU K Y , ZHU X , SUN S H , et al . Inhibition of TLR4 prevents hippocampal hypoxic⁃ischemic injury by regulating ferroptosis in neonatal rats [J ] . Exp Neurol , 2021 , 345 : 113828 .

PARK M W , CHA H W , KIM J , et al . NOX4 promotes ferroptosis of astrocytes by oxidative stress⁃induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases [J ] . Redox Biol , 2021 , 41 : 101947 .

KWON M Y , PARK E , LEE S J , et al . Heme oxygenase⁃1 accelerates erastin⁃induced ferroptotic cell death [J ] . Oncotarget , 2015 , 6 ( 27 ): 24393 ⁃ 24403 .

YANG W S , SRIRAMARATNAM R , WELSCH M E , et al . Regulation of ferroptotic cancer cell death by GPX4 [J ] . Cell , 2014 , 156 ( 12 ): 317 ⁃ 331 .

ZHENG L T , QIN S S , SI W , et al . Pan⁃cancer single⁃cell landscape of tumor⁃infiltrating T cells [J ] . Science , 2021 , 374 ( 6574 ): abe6474 .

KANG J H , ZAPPASODI R . Modulating Treg stability to improve cancer immunotherapy [J ] . Trends Cancer , 2023 , 9 ( 11 ): 911 ⁃ 927 .

WONG H S , PARK K , GOLA A , et al . A local regulatory T cell feedback circuit maintains immune homeostasis by pruning self⁃activated T cells [J ] . Cell , 2021 , 184 ( 15 ): 3981 ⁃ 3997 .e22.

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