山东大学学报 (医学版) ›› 2024, Vol. 62 ›› Issue (7): 21-32.doi: 10.6040/j.issn.1671-7554.0.2024.0114
王静1,刘晓菲2,曾荣3,许长娟2,张锦涛2,董亮2,3
WANG Jing1, LIU Xiaofei2, ZENG Rong3, XU Changjuan2, ZHANG Jintao2, DONG Liang2,3
摘要: 目的 通过生物信息学分析的方法识别和验证哮喘中潜在的坏死性凋亡相关基因(necroptosis-related genes, NRGs)。 方法 基因表达综合(Gene Expression Omnibus, GEO)数据库提供了基因表达谱数据集GSE76262,并使用R软件筛选潜在的差异表达NRGs。对差异表达的 NRGs进行蛋白质-蛋白质相互作用(protein-protein interaction, PPI)分析、基因本体论(gene ontology, GO)富集分析、京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)通路富集分析。通过最小绝对收缩和选择算子(least absolute shrinkage and selection operator, LASSO)逻辑回归和支持向量机递归特征消除(support vector machine-recursive feature elimination, SVM-RFE)算法分析上调的NRGs。共同特征基因被确定为潜在的诊断标志物,并绘制受试者特征(receiver operator characteristic, ROC)曲线以验证其诊断效能。GSE137268进一步验证筛选出的特征基因的表达情况和诊断效能。使用在线工具预测可以靶向调控特征基因表达的微小RNAs(microRNAs, miRNAs)。 结果 在118例哮喘患者和21名健康对照者中鉴定出33个差异表达的 NRGs(13个上调和20个下调)。PPI结果提示20 个差异表达的 NRGs相互作用。GO和KEGG富集分析显示NRGs与多个信号通路、淋巴细胞激活、细胞凋亡和免疫调节等相关。LASSO和SVM-RFE筛选出 7 个上调的 NRGs 可作为潜在的诊断基因,其ROC曲线显示出较高的诊断效率,曲线下面积(area under the curve, AUC)高于0.7。经GSE137268验证,7个特征基因与训练集的表达趋势相同(AUC>0.65)。预测hsa-miR-138-5p、hsa-miR-200b-3p和hsa-miR-30e-5p可调控哮喘患者NRGs的表达。 结论 BIRC3、HIF1A、FLOT1、NLRP3、RIPK2、GBE1和PELI1为哮喘的潜在生物标志物。Hsa-miR-138-5p、hsa-miR-200b-3p和hsa-miR-30e-5p分别是HIF1A、RIPK2和PELI1的上游调节因子。
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