中低剂量电离辐射对甲状腺乳头状癌免疫微环境的影响  

Impact of low-to-moderate dose ionizing radiation on the immune microenvironment of papillary thyroid carcinoma

作　　者：李哲成 唐能[1] 姚磊 吴昭颐 王志明[1] LI Zhecheng;TANG Neng;YAO Lei;WU Zhaoyi;WANG Zhiming(Department of General Surgery,Xiangya Hospital,Central South University,Changsha 410008,China;Department of Thyroid and Breast Surgery,Hunan Provincial People's Hospital(the First Affiliated Hospital of Hunan Normal University),Changsha 410005,China)

机构地区：[1]中南大学湘雅医院普通外科,湖南长沙410008 [2]湖南省人民医院(湖南师范大学附属第一医院)乳甲外科,湖南长沙410005

出　　处：《中国普通外科杂志》2025年第2期346-355,共10页China Journal of General Surgery

摘　　要：背景与目的:甲状腺乳头状癌(PTC)作为最常见的甲状腺癌类型,其发病率在全球范围内快速增长,对个体健康和社会公共卫生体系构成严重威胁。中低剂量电离辐射的暴露场景与普通人群的日常生活更为贴近,因而更容易引发公共卫生问题,且已经被广泛认为可能对免疫系统造成重构性影响。本研究探讨中低剂量电离辐射对PTC肿瘤免疫微环境的影响,旨在揭示这类辐射暴露事件对PTC患者的潜在危害。方法:从GEO数据库中检索并下载了包含RNA-seq数据及相应临床病例资料的两个数据集(GSE29265和GSE35570)。这两个数据集均源自因切尔诺贝利核电站事故而暴露于电离辐射的甲状腺癌患者以及散发甲状腺癌患者的样本。通过数据清洗、合并及去批次效应后,利用R语言进行差异表达基因分析、功能富集分析、免疫细胞浸润分析以及肿瘤微环境分析。结果:在肿瘤样本中,辐射暴露组相较于散发组有3个基因表达明显上调,27个基因表达明显下调。这些差异表达基因主要富集在与免疫反应密切相关的生物学功能上,包括趋化因子活动、多种免疫细胞趋化作用及肿瘤免疫等。免疫细胞浸润分析显示,在正常样本中,辐射暴露对免疫细胞浸润的影响有限;但在肿瘤样本中,辐射暴露组的免疫评分和ESTIMATE评分均明显低于散发组。进一步分析发现,辐射暴露组中总T细胞、CD4^(+)T细胞、CD8^(+)T细胞、B细胞和细胞毒性淋巴细胞在肿瘤微环境中的浸润水平明显低于散发组。结论:尽管中低剂量电离辐射对正常甲状腺组织的影响相对较小,但在PTC肿瘤微环境中,辐射暴露显著降低了多种免疫细胞亚型的浸润程度,这可能对疾病的进展产生重要影响。Background and Aims:Papillary thyroid carcinoma(PTC),the most common type of thyroid cancer,has been rapidly increasing in incidence worldwide,posing a serious threat to individual health and public healthcare systems.Exposure to low-to-moderate doses of ionizing radiation is more relevant to the daily lives of the general population and,therefore,raises greater public health concerns.It has also been widely recognized as a potential factor in immune system remodeling.This study was conducted to investigate the impact of low-to-moderate dose ionizing radiation on the tumor immune microenvironment of PTC,aiming to reveal the potential hazards of such radiation exposure in PTC patients.Methods:Two datasets(GSE29265 and GSE35570)containing RNA-seq data and corresponding clinical information were retrieved and downloaded from the GEO database.These datasets included thyroid cancer samples from patients exposed to ionizing radiation due to the Chernobyl disaster,as well as sporadic thyroid cancer cases.After data cleaning,merging,batch effect correction,differential gene expression analysis,functional enrichment analysis,immune cell infiltration analysis,and tumor microenvironment analysis were performed using R language.Results:In tumor samples,the radiation-exposed group exhibited significant differential gene expression compared to the sporadic group,with three genes upregulated and 27 genes downregulated.These differentially expressed genes were primarily enriched in biological functions closely related to immune responses,including chemokine activity,immune cell chemotaxis,and tumor immunity.Immune cell infiltration analysis indicated that radiation exposure had a limited impact on immune cell infiltration in normal samples.However,in tumor samples,the immune and ESTIMATE scores were significantly lower in the radiation-exposed group than in the sporadic group.Further analysis revealed that total T cells,CD4^(+)T cells,CD8^(+)T cells,B cells,and cytotoxic lymphocytes exhibited significantly lower infiltration lev

关 键 词：甲状腺肿瘤 癌 乳头状 辐射 电离 免疫微环境 

分 类 号：R736.1[医药卫生—肿瘤]