基于生物信息学方法探讨阿尔茨海默病患者内嗅皮质组织中的免疫浸润变化  

Investigating the changes of immune infiltration in the entorhinal cortex of Alzheimer's patients based on bioinformatics analysis

作　　者：邢诗曼 杨士运 周欣梅[2] 文晓东[2] 童汪霞[3] 罗宁 XING Shi-man;YANG Shi-yun;ZHOU Xin-mei;无(Graduate School of Guangxi University of Chinese Medicine,Nanning 530010,China;Department of Neurology,Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine,Nanning 530011,China;Department of Hepatology,Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine,Nanning 530011,China)

机构地区：[1]广西中医药大学研究生院,广西南宁530010 [2]广西中医药大学附属瑞康医院神经内科,广西南宁530011 [3]广西中医药大学附属瑞康医院肝病内科,广西南宁530011

出　　处：《吉林医学》2023年第6期1431-1438,共8页Jilin Medical Journal

基　　金：国家自然科学基金项目(82060843,82260860);广西自然科学基金项目(2021GXNSFAA196031)。

摘　　要：目的:探讨阿尔茨海默病(AD)患者内嗅皮质组织样本中免疫浸润的变化。方法:从高通量基因表达(GEO)数据库下载AD患者内嗅皮质的数据集。使用Rlimma软件包对差异基因进行鉴定。通过功能注释和富集分析探讨差异基因生物学功能。用无监督聚类及单样本免疫浸润分析观察聚类模式所对应的免疫浸润类型。结果:共获得642个差异基因以及是否进展为AD相关的A、B聚类模式。A模式富集了9例正常对照样本及1例AD样本。B模式富集了10例AD样本。B模式相较A模式对应较低的简易精神状态检查评分及较高级别的Braak分期。单样本免疫浸润分析显示γδT细胞、巨噬细胞以及1型辅助T细胞增多。基因集变异分析显示B模式富集了移植物抗宿主疾病、同种异体移植物排斥、抗原加工及提呈等免疫相关通路。最后确定了6个因子用于风险模型的构建,预测模型训练集和验证集的受试者工作特征(ROC)曲线分别达到1.0和0.921。结论:AD患者内嗅皮质中存在明显的免疫炎症表现,免疫炎症作为重要因素参与了AD的疾病过程。Objective To investigate the changes of immune infiltration in entorhinal cortex tissue samples from patients with Alzheimer's disease.Method Dataset of AD patients'entorhinal cortex was downloaded from the GEO database.Differentially expressed genes were identified using the Rlimma software package.Its biological functions were explored through functional annotation and enrichment analysis.Unsupervised clustering and ssGSEA analysis were used to observe the types of immune infiltration corresponding to the clustering patterns.Results A total of 642 differential genes and A and B cluster patterns related to progression to Alzheimer's disease were obtained.In the A mode,9 control samples and 1 AD sample were enriched.The B mode enriched 10 AD samples.Mode B corresponds to lower MMSE scores and higher Braakstage staging than mode A.ssGSEA immune infiltration analysis showed an increase inγ-δT cells,macrophages and type 1 helper T cells.GSVA enrichment analysis showed that the B pattern was enriched in immune-related pathways such as graft-versus-host disease,allograft rejection,antigen processing and presentation.Finally,6 fctors had been determined by Multiple Stepwise Cox Regression Analysis(Cox)to construct the hazard model.The receiver operating characteristic(ROC)curves of the training set and validation set of the subsequently constructed prediction model reached 1.0 and 0.921,respectively.Conclusion There are obvious manifestations of immune inflammation in the entorhinal cortex of AD patients.As an important factor,immune inflammation is involved in the disease process of AD.

关 键 词：阿尔茨海默病 免疫浸润 内嗅皮质 生物信息分析 

分 类 号：R749.16[医药卫生—神经病学与精神病学] Q811.4[医药卫生—临床医学]