克罗恩病和牙周炎的共有免疫相关基因及其作为诊断生物标志物的潜力  

Immune-related genes shared between Crohn's disease and periodontitis and their potential as diagnostic

作　　者：张志豪 杨益[2] 王月秋[3] 孙思怡 陈虹 舒菲 刘梅[1] ZHANG Zhihao;YANG Yi;WANG Yueqiu;SUN Siyi;CHEN Hong;SHU Fei;LIU Mei(Department of Prosthodontics,The Affiliated Stomatological Hospital of Nanjing Medical University,Jiangsu Province Key Laboratory of Oral Diseases,Jiangsu Province Engineering Research Center of Stomatological Translational Medicine,Nanjing 210029,China)

机构地区：[1]南京医科大学附属口腔医院修复科,江苏省口腔疾病研究重点实验室,江苏省口腔转化医学工程研究中心,江苏南京210029 [2]南京医科大学附属口腔医院种植科,江苏省口腔疾病研究重点实验室,江苏省口腔转化医学工程研究中心,江苏南京210029 [3]南京医科大学附属口腔医院牙体牙髓科,江苏省口腔疾病研究重点实验室,江苏省口腔转化医学工程研究中心,江苏南京210029 [4]南京医科大学附属口腔医院综合科,江苏省口腔疾病研究重点实验室,江苏省口腔转化医学工程研究中心,江苏南京210029

出　　处：《口腔医学》2024年第3期184-191,共8页Stomatology

基　　金：江苏省科技教能力提升项目——江苏省研究院培养单位(YJXYYJSDW4);江苏省医疗创新项目(CXZX202227)。

摘　　要：目的通过研究牙周炎和克罗恩病(Crohn's disease,CD)的共有免疫相关基因,探讨两种疾病间的共同病理生理学,并评估相关基因作为诊断生物标志物的价值。方法从GEO数据库下载CD和牙周炎的基因表达数据。对数据预处理后进行差异表达分析以获得差异表达基因(differentially expressed genes,DEGs),然后对共同DEGs进行功能富集和疾病本体分析并构建蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络。对CD和牙周炎数据库进行加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)以确定与疾病最相关的关键模块,从而进一步筛选出串扰基因,通过单样本基因集浓缩分析(ssGSEA)对CD和牙周炎的免疫细胞图谱进行评估,筛选CD和牙周炎中与免疫最相关的基因构建诊断模型,并在验证数据集中验证其准确性。结果共鉴定出143个共同DEGs,功能富集分析强调免疫在CD和牙周炎中发挥重要作用。通过WGCNA分析得到11个串扰基因,随后免疫浸润分析最终确定了4个与CD、牙周炎和免疫相关的基因(HLA-DMA、CD38、PIM2、TGM2);使用这4个基因构建的诊断模型在训练数据集和外部验证数据集中都具有良好的诊断性能。结论HLA-DMA、CD38、PIM2、TGM2基因参与了CD和牙周炎的发生发展,在免疫反应中扮演重要角色,以这4个基因构建的诊断模型对两种疾病都有良好的诊断效力。Objective To investigate shared immune-related genes between periodontitis and Crohn's disease(CD),explore their common pathophysiology,and assess the value of relevant genes as diagnostic biomarkers.Methods Gene expression data for CD and periodontitis were obtained from the GEO database.After data preprocessing,differential expression analysis was performed to identify differentially expressed genes(DEGs).Functional enrichment and disease ontology analysis were conducted on the common DEGs,and a protein-protein interaction(PPI)network was constructed.Weighted gene co-expression network analysis(WGCNA)was applied to the CD and periodontitis databases to determine key modules most relevant to the diseases.Perturbation genes were further selected.Immunocyte profiles in CD and periodontitis were assessed using single-sample gene set enrichment analysis(ssGSEA).A diagnostic model for CD and periodontitis,based on genes most associated with immunity,was constructed and validated using an independent dataset.Results A total of 143 common differentially expressed genes were identified.Functional enrichment analysis highlighted the significant role of immunity in both CD and periodontitis.WGCNA analysis identified 11 perturbation genes,and subsequent immune infiltration analysis revealed four genes(Genes HLA-DMA,CD38,PIM2 and TGM2)closely associated with CD,periodontitis and immune response.The diagnostic model built using these four genes demonstrated excellent diagnostic performance in both the training and external validation datasets.Conclusion Genes HLA-DMA,CD38,PIM2 and TGM2 are involved in the development of CD and periodontitis,playing crucial roles in immune responses.The diagnostic model constructed with these four genes exhibits strong diagnostic efficacy for both diseases.

关 键 词：免疫 诊断 牙周炎 克罗恩病 生物标志物 生物信息学 

分 类 号：R574[医药卫生—消化系统] R781.4[医药卫生—内科学]