{"title":"牙周炎潜在免疫标志物和治疗靶点的遗传分析。","authors":"Hui Li, Wanqing Du, Xin Ye, Xi Luo, Xuejing Duan","doi":"10.3389/fdmed.2024.1480346","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Periodontitis is a chronic inflammatory periodontal disease resulting in destroyed periodontal tissue. Many studies have found that the host's inflammatory immune responses are involved in the risk of periodontal tissue damage. In this study, we aim to identify potential biomarkers and therapeutic targets related to immunity in periodontitis.</p><p><strong>Methods: </strong>GSE16134 and GSE10334 were downloaded from the Gene Expression Omnibus (GEO) database, and the immune-related genes were obtained from the Immunology Database and Analysis Portal (ImmPort). After the differentially expressed immune-related genes (DE-IRGs) were identified, enrichment analysis was performed. Two machine learning methods, the least absolute shrinkage and selector operation (LASSO) logistic regression and the support vector machine-recursive feature elimination (SVM-RFE), were used to screen out potential markers for the diagnosis of periodontitis. The CIBERSORT algorithm and LM22 matrix were used to analyze the percentage of infiltrating immune cells in periodontitis. Finally, the potential drug targets for the selected immune-related marker genes were predicted using relevant databases.</p><p><strong>Results: </strong>A total of 7 genes (CD19, CXCR4, FABP4, FOS, IGHD, IL2RG, and PPBP) were upregulated in periodontitis samples. The area under the receiver operating characteristic curve (AUC) value of only one gene for distinguishing periodontitis from healthy samples ranged from 0.724 to 0.894. The prediction ability of the combined risk score of these 7 DE-IRGs was improved (AUC = 0.955). Naïve B cells, neutrophils, plasma cells, and activated memory CD4 T cells were significantly enriched in periodontitis samples, and 25 drugs targeting 4 DE-IRGs were predicted.</p><p><strong>Conclusion: </strong>We developed a diagnostic model based on seven IRGs for periodontitis. The possible drugs targeting IRGs may provide new ideas for periodontitis treatment.</p>","PeriodicalId":73077,"journal":{"name":"Frontiers in dental medicine","volume":"5 ","pages":"1480346"},"PeriodicalIF":1.5000,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797874/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genetic analysis of potential markers and therapeutic targets for immunity in periodontitis.\",\"authors\":\"Hui Li, Wanqing Du, Xin Ye, Xi Luo, Xuejing Duan\",\"doi\":\"10.3389/fdmed.2024.1480346\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Periodontitis is a chronic inflammatory periodontal disease resulting in destroyed periodontal tissue. Many studies have found that the host's inflammatory immune responses are involved in the risk of periodontal tissue damage. In this study, we aim to identify potential biomarkers and therapeutic targets related to immunity in periodontitis.</p><p><strong>Methods: </strong>GSE16134 and GSE10334 were downloaded from the Gene Expression Omnibus (GEO) database, and the immune-related genes were obtained from the Immunology Database and Analysis Portal (ImmPort). After the differentially expressed immune-related genes (DE-IRGs) were identified, enrichment analysis was performed. Two machine learning methods, the least absolute shrinkage and selector operation (LASSO) logistic regression and the support vector machine-recursive feature elimination (SVM-RFE), were used to screen out potential markers for the diagnosis of periodontitis. The CIBERSORT algorithm and LM22 matrix were used to analyze the percentage of infiltrating immune cells in periodontitis. Finally, the potential drug targets for the selected immune-related marker genes were predicted using relevant databases.</p><p><strong>Results: </strong>A total of 7 genes (CD19, CXCR4, FABP4, FOS, IGHD, IL2RG, and PPBP) were upregulated in periodontitis samples. The area under the receiver operating characteristic curve (AUC) value of only one gene for distinguishing periodontitis from healthy samples ranged from 0.724 to 0.894. The prediction ability of the combined risk score of these 7 DE-IRGs was improved (AUC = 0.955). Naïve B cells, neutrophils, plasma cells, and activated memory CD4 T cells were significantly enriched in periodontitis samples, and 25 drugs targeting 4 DE-IRGs were predicted.</p><p><strong>Conclusion: </strong>We developed a diagnostic model based on seven IRGs for periodontitis. The possible drugs targeting IRGs may provide new ideas for periodontitis treatment.</p>\",\"PeriodicalId\":73077,\"journal\":{\"name\":\"Frontiers in dental medicine\",\"volume\":\"5 \",\"pages\":\"1480346\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-11-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11797874/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in dental medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3389/fdmed.2024.1480346\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in dental medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/fdmed.2024.1480346","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
引用次数: 0
摘要
目的:牙周炎是一种导致牙周组织破坏的慢性炎症性牙周病。许多研究发现,宿主的炎症免疫反应与牙周组织损伤的风险有关。在这项研究中,我们的目标是确定与牙周炎免疫相关的潜在生物标志物和治疗靶点。方法:从Gene Expression Omnibus (GEO)数据库下载GSE16134和GSE10334,从Immunology database and Analysis Portal (import)获取免疫相关基因。鉴定出差异表达免疫相关基因(DE-IRGs)后,进行富集分析。使用最小绝对收缩和选择操作(LASSO)逻辑回归和支持向量机递归特征消除(SVM-RFE)两种机器学习方法筛选牙周炎诊断的潜在标志物。采用CIBERSORT算法和LM22基质分析牙周炎组织中浸润免疫细胞的百分比。最后,利用相关数据库预测所选免疫相关标记基因的潜在药物靶点。结果:在牙周炎样本中,共有7个基因(CD19、CXCR4、FABP4、FOS、IGHD、IL2RG和PPBP)表达上调。仅一种基因用于牙周炎与健康样品鉴别的受试者工作特征曲线下面积(AUC)值在0.724 ~ 0.894之间。7种DE-IRGs的综合风险评分预测能力均有提高(AUC = 0.955)。Naïve牙周炎样本中B细胞、中性粒细胞、浆细胞和活化记忆CD4 T细胞显著富集,预测25种药物靶向4种DE-IRGs。结论:建立了基于7种IRGs的牙周炎诊断模型。靶向IRGs的药物可能为牙周炎的治疗提供新的思路。
Genetic analysis of potential markers and therapeutic targets for immunity in periodontitis.
Objective: Periodontitis is a chronic inflammatory periodontal disease resulting in destroyed periodontal tissue. Many studies have found that the host's inflammatory immune responses are involved in the risk of periodontal tissue damage. In this study, we aim to identify potential biomarkers and therapeutic targets related to immunity in periodontitis.
Methods: GSE16134 and GSE10334 were downloaded from the Gene Expression Omnibus (GEO) database, and the immune-related genes were obtained from the Immunology Database and Analysis Portal (ImmPort). After the differentially expressed immune-related genes (DE-IRGs) were identified, enrichment analysis was performed. Two machine learning methods, the least absolute shrinkage and selector operation (LASSO) logistic regression and the support vector machine-recursive feature elimination (SVM-RFE), were used to screen out potential markers for the diagnosis of periodontitis. The CIBERSORT algorithm and LM22 matrix were used to analyze the percentage of infiltrating immune cells in periodontitis. Finally, the potential drug targets for the selected immune-related marker genes were predicted using relevant databases.
Results: A total of 7 genes (CD19, CXCR4, FABP4, FOS, IGHD, IL2RG, and PPBP) were upregulated in periodontitis samples. The area under the receiver operating characteristic curve (AUC) value of only one gene for distinguishing periodontitis from healthy samples ranged from 0.724 to 0.894. The prediction ability of the combined risk score of these 7 DE-IRGs was improved (AUC = 0.955). Naïve B cells, neutrophils, plasma cells, and activated memory CD4 T cells were significantly enriched in periodontitis samples, and 25 drugs targeting 4 DE-IRGs were predicted.
Conclusion: We developed a diagnostic model based on seven IRGs for periodontitis. The possible drugs targeting IRGs may provide new ideas for periodontitis treatment.