基于生物信息学的结核病铁死亡相关基因MT1G的筛选与鉴定

doi:10.19982/j.issn.1000-6621.20250387

中国防痨杂志 ›› 2026, Vol. 48 ›› Issue (3): 366-376.doi: 10.19982/j.issn.1000-6621.20250387

基于生物信息学的结核病铁死亡相关基因MT1G的筛选与鉴定

高岩¹, 彭英杰², 葛萧¹, 徐健¹, 刘晓华³, 刘金龙¹(), 王媛媛⁴()

¹山东省潍坊市妇幼保健院检验科,北京大学医学部-潍坊市妇幼健康联合研究中心,潍坊医学院儿科研究所,潍坊 261011
²潍坊市人民医院神经内五科,潍坊 261000
³山东省潍坊市中心血站血供科,潍坊 261000
⁴山东省潍坊市妇幼保健院儿五科,潍坊 261011

收稿日期:2025-09-24 出版日期:2026-03-10 发布日期:2026-03-06
通信作者: 刘金龙,王媛媛 E-mail:jinglong6289@126.com;okboy-6238111@163.com
基金资助:
山东省医药卫生科技项目(202402081104);山东省医学会科研项目(YXH2024QS056);潍坊市卫生健康委员会科研项目(WFWSJK-2025-094);潍坊市科技发展计划项目(2024YX065);北京大学医学部-潍坊市妇幼健康联合研究中心经费支持

Screening and identification of iron death-related gene MT1G in tuberculosis based on bioinformatics

Gao Yan¹, Peng Yingjie², Ge Xiao¹, Xu Jian¹, Liu Xiaohua³, Liu Jinlong¹(), Wang Yuanyuan⁴()

¹Department of Laboratory, Weifang Maternal and Child Health Hospital, Peking University Health Science Center-Weifang Joint Research Center for Maternal and Child Health, Institute of Pediatrics, Weifang Medical University, Weifang 261011, China
²Department of Neurology 5, Weifang People’s Hospital, Weifang 261000, China
³Department of Blood Supply, Weifang Central Blood Center, Weifang 261000, China
⁴Department of Pediatrics V, Weifang Maternal and Child Health Hospital, Weifang 261011, China

Received:2025-09-24 Online:2026-03-10 Published:2026-03-06
Contact: Liu Jinlong,Wang Yuanyuan E-mail:jinglong6289@126.com;okboy-6238111@163.com
Supported by:
Shandong Province Medical and Health Science and Technology Project(202402081104);Shandong Medical Association Research Project(YXH2024QS056);Weifang Municipal Health Commission Research Project(WFWSJK-2025-094);Weifang Science and Technology Development Plan Project(2024YX065);Funding Support from the Peking University Health Science Center-Weifang Maternal and Child Health Joint Research Center

摘要/Abstract

摘要：

目的: 基于生物信息学分析与铁死亡相关的结核病差异表达基因,以筛选潜在的结核病诊断标志物。方法: 首先通过免疫组化(肺组织切片来源于潍坊市妇幼保健院6例肺结核患者)验证铁死亡相关标志物FACL4在结核病中的表达,再基于在线公共基因表达数据库(GEO数据库)筛选结核病相关差异表达基因,并运用生物信息学分析技术进行京都基因与基因组百科全书和基因本体富集分析及免疫微环境验证;然后将筛选出的结核病差异表达基因与数据库中铁死亡相关基因集取交集,得到与铁死亡相关的结核病候选基因集并进行富集分析;为得到差异显著且更一致的高表达关键基因,进一步将结核病样本分为C1和C2亚型,通过聚类和差异性分析进行差异基因的再筛选,得到关键基因;最后使用在线数据集、免疫组化、免疫荧光和RT-PCR验证关键基因表达。结果: 免疫组化结果显示,FACL4在肺结核组织中高表达。从GEO数据库中筛选出1142个结核病相关差异基因,均富集于免疫相关通路,且均与免疫微环境密切相关。从在线数据库中筛选出438个铁死亡相关基因,将其与1142个结核病相关差异基因中上调的624个差异基因进行交集匹配,共获得52个共同的铁死亡相关差异基因;再将52个铁死亡相关基因的结核感染样本分为C1和C2亚型进行差异基因的再筛选,最终筛选出MT1G、CDH1、IL1β和PTGS2等4个关键候选基因。经在线数据集、免疫组化、免疫荧光和RT-PCR验证,最终确定MT1G基因表达显著升高,具有良好诊断价值。结论: 初步验证了铁死亡相关基因MT1G作为结核病潜在生物标志物的可能性,为探索铁死亡在结核病免疫病理机制和治疗耐药结核病提供了新的策略。

关键词: 结核, 铁蛋白质类, 细胞死亡, 分子生物学, 基因表达

Abstract:

Objective: To identify potential diagnostic biomarkers for tuberculosis by screening ferroptosis-related differentially expressed genes in tuberculosis through bioinformatics methods. Methods: Firstly, the expression of the ferroptosis-related marker FACL4 in tuberculosis was validated by immunohistochemistry using lung tissue sections from 6 pulmonary tuberculosis patients collected at Weifang Maternal and Child Health Hospital. Then, tuberculosis-associated differentially expressed genes were screened from the Gene Expression Omnibus (GEO) database, followed by bioinformatics analysis including kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis and immune microenvironment validation. Next, the tuberculosis-related differentially expressed genes were intersected with the ferroptosis-related gene set to obtain a set of candidate genes associated with ferroptosis in tuberculosis, followed by enrichment analysis. To identify significantly and consistently high-expressed key genes, tuberculosis samples were further stratified into C1 and C2 molecular subtypes, and subtype-specific differentially expressed genes were re-screened using clustering and differential analysis. Finally, key gene expression was validated using online datasets, immunohistochemistry, immunofluorescence, and RT-PCR. Results: Immunohistochemical results showed that FACL4 was highly expressed in pulmonary tuberculosis tissues. A total of 1142 tuberculosis-associated differentially expressed genes were identified from the GEO database, all enriched in immune-related pathways and closely linked to immune microenvironment. A set of 438 ferroptosis-related genes was screened, and their intersection with the 624 upregulated tuberculosis-related differential genes resulted in 52 common ferroptosis-related differential genes. Further the 52 genes in tuberculosis samples were further screened into C1 and C2 subtypes for differential gene identification, ultimately identified 4 key candidate genes: MT1G, CDH1, IL1β, and PTGS2. RT-PCR, immunohistochemistry, and immunofluorescence confirmed that MT1G was significantly upregulated supporting its potential as a diagnostic biomarker. Conclusion: This study preliminarily validated the potential of the ferroptosis-related gene MT1G as a biomarker for tuberculosis, providing new strategies for exploring the immuno-pathological mechanisms of tuberculosis and the treatment of drug-resistant tuberculosis.

Key words: Tuberculosis, Ferritins, Cell death, Molecular biology, Gene expression

中图分类号:

R373.1

高岩, 彭英杰, 葛萧, 徐健, 刘晓华, 刘金龙, 王媛媛. 基于生物信息学的结核病铁死亡相关基因MT1G的筛选与鉴定[J]. 中国防痨杂志, 2026, 48(3): 366-376. doi: 10.19982/j.issn.1000-6621.20250387

Gao Yan, Peng Yingjie, Ge Xiao, Xu Jian, Liu Xiaohua, Liu Jinlong, Wang Yuanyuan. Screening and identification of iron death-related gene MT1G in tuberculosis based on bioinformatics[J]. Chinese Journal of Antituberculosis, 2026, 48(3): 366-376. doi: 10.19982/j.issn.1000-6621.20250387

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基因	正向引物(5'-3')	反向引物(5'-3')
MT1G	GCTGCTGCTCCTGCTGCC	TTCAAGTCAAAATTGTTTTATTGTCAC
GAPDH	CAGGTGGTCTCCTCTGACTTCAAC	TCTCTTCCTCTTGTGCTCTTGCTG

基因	HC组	TB组	t值	P值
IL1β	7.384±0.238	9.780±0.049	-17.051	<0.001
CDH1	3.134±0.129	3.117±0.173	0.137	0.898
PTGS2	5.286±0.120	5.516±0.107	-2.480	0.069
MT1G	4.668±0.139	5.576±0.024	-11.142	<0.001

基于生物信息学的结核病铁死亡相关基因MT1G的筛选与鉴定

Screening and identification of iron death-related gene MT1G in tuberculosis based on bioinformatics

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