首页|期刊导航|检验医学与临床|铁死亡相关基因作为克罗恩病诊断生物标志物的价值

铁死亡相关基因作为克罗恩病诊断生物标志物的价值OA

The value of ferroptosis-related genes as diagnostic biomarkers for Crohn's disease

中文摘要英文摘要

目的 探讨铁死亡相关基因作为克罗恩病(CD)诊断生物标志物的价值.方法 从GEO数据库选取了 3个CD相关的基因表达矩阵作为研究对象,在排除测序组织非回肠部位的标本后,最终共纳入402例CD患者作为CD组,63例健康体检者作为对照组.另选取2022年1月至2024年12月于该院就诊的12例CD患者作为临床CD组,其中8例患者同时留存有病变旁无炎症的正常肠黏膜组织冻存标本,将其作为配对对照组进行分析.从GEO数据库下载并整合3个CD相关转录组数据集,批次效应校正后筛选CD与健康对照者之间的差异表达基因(DEGs),与铁死亡相关基因取交集筛选得到关键共有基因.开展功能富集分析、蛋白质互作网络构建及核心基因表达验证,并利用6种算法对基因进行排序.采用受试者工作特征(ROC)曲线分析6个在所有6种算法中均排名靠前且排名高度一致的基因对CD的诊断价值.结果 共筛选出607个DEGs,鉴定出32个关键共有基因,其中16个为驱动基因,14个为抑制基因,2个为标记基因.京都基因与基因百科全书富集分析结果显示,前10个显著通路主要涉及铁死亡、脂肪酸合成、泛醌和萜醌合成、非洲锥虫病、抗叶酸耐药、脂肪酸降解、移植物抗宿主病、精氨酸合成、白细胞介素-17(IL-17)信号通路、疟疾.通过蛋白质互作网络筛选出谷胱甘肽过氧化物酶4(GPX4)、缺氧诱导因子-1α(HIF-1α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、脂质运载蛋白2(LCN2)、前列腺素内过氧化物合成酶2(PTGS2)6个关键枢纽基因.CD组GPX4信使 RNA(mRNA)水平低于对照组,HIF-1α mRNA、IL-1β mRNA、IL-6 mRNA、LCN2 mRNA 和 PTGS2 mR-NA水平高于对照组,差异均有统计学意义(P<0.05).ROC曲线分析结果显示,GPX4、HIF-1α、IL-1β、IL-6、LCN2、PTGS2 单独诊断 CD 的曲线下面积(AUC)分别为 0.776、0.826、0.853、0.716、0.891、0.780.临床 CD组 GPX4 mRNA 水平低于配对对照组,HIF-1α mRNA、IL-1β mRNA、IL-6 mRNA、LCN2 mRNA、PTGS2 mRNA水平高于配对对照组,差异均有统计学意义(P<0.05).结论 该研究系统鉴定了在CD中差异表达的铁死亡关键基因,揭示其潜在的疾病机制,具有良好的诊断效能,能为CD的精准诊疗提供新的思路和候选靶标.

Objective To explore the value of ferroptosis-related genes as diagnostic biomarkers for Crohn's disease(CD).Methods Three gene expression matrices related to CD were selected from the GEO data-base.After excluding specimens from non-ileal parts of the sequenced tissues,a total of 402 CD patients were included as the CD group and 63 healthy individuals as the control group.Additionally,12 CD patients who visited the hospital from January 2022 to December 2024 were selected as the clinical CD group,among which 8 patients also had normal intestinal mucosal tissues without inflammation adjacent to the lesion,which were frozen and preserved for analysis as the paired control group.The three CD-related transcriptome datasets were downloaded from the GEO database and integrated after batch effect correction.The differentially ex-pressed genes(DEGs)between CD and healthy controls were screened,and the intersection with ferroptosis-related genes was taken to obtain the key common genes.Functional enrichment analysis,protein interaction network construction and core gene expression verification were carried out,and six algorithms were utilized to sort the genes.The diagnostic value of six genes that ranked highly and consistently across all six algo-rithms for CD was analyzed using the receiver operating characteristic(ROC)curve.Results A total of 607 DEGs were screened out,and 32 key common genes were identified,among which 16 were driver genes,14 were inhibitory genes,and 2 were marker genes.The Kyoto encyclopedia of genes and genomes enrichment a-nalysis showed that the top 10 significant pathways mainly involved ferroptosis,fatty acid synthesis,ubiqui-none and terpenoid synthesis,African trypanosomiasis,antifolate resistance,fatty acid degradation,graft-ver-sus-host disease,arginine synthesis,interleukin-17(IL-17)signaling pathway and malaria.Six key hub genes including glutathione peroxidase 4(GPX4),hypoxia-inducible factor-1α(HIF-1α),interleukin-1β(IL-1β),in-terleukin-6(IL-6),lipoprotein transporter 2(LCN2)and prostaglandin endoperoxide synthase 2(PTGS2)were screened out through the protein-protein interaction network.The messenger RNA(mRNA)level of GPX4 in the CD group was lower than that in the control group,while the mRNA levels of HIF-1α,IL-1β,IL-6,LCN2 and PTGS2 were higher than those in the control group,and the differences were statistically signifi-cant(P<0.05).The ROC curve analysis showed that the areas under the curve(AUC)for GPX4,HIF-1α,IL-1β,IL-6,LCN2 and PTGS2 alone for diagnosing CD were 0.776,0.826,0.853,0.716,0.891 and 0.780 re-spectively.The GPX4 mRNA level in the clinical CD group was lower than that in the paired control group,while the levels of HIF-1α mRNA,IL-1β mRNA,IL-6 mRNA,LCN2 mRNA and PTGS2 mRNA were higher than those in the paired control group,and the differences were statistically significant(P<0.05).Conclusion This study systematically identifies the key genes involved in ferroptosis that are differentially expressed in CD,reveals their potential disease mechanisms,and has good diagnostic efficacy.It can provide new ideas and candidate targets for the precise diagnosis and treatment of CD.

马雨萱;张柳溪;张浩;卢瑗瑗

空军军医大学西京医院国家消化系统疾病临床医学研究中心和消化系肿瘤整合防治全国重点实验室,陕西西安 710032空军军医大学西京医院国家消化系统疾病临床医学研究中心和消化系肿瘤整合防治全国重点实验室,陕西西安 710032空军军医大学西京医院国家消化系统疾病临床医学研究中心和消化系肿瘤整合防治全国重点实验室,陕西西安 710032空军军医大学西京医院国家消化系统疾病临床医学研究中心和消化系肿瘤整合防治全国重点实验室,陕西西安 710032

医药卫生

克罗恩病铁死亡差异基因诊断

Crohn's diseaseferroptosisdifferentially expressed genediagnosis

《检验医学与临床》 2026 (9)

1177-1182,6

国家自然科学基金项目(82425046822731428222205882573226).

10.3969/j.issn.1672-9455.2026.09.005

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