非特异性间质性肺炎关键基因与免疫细胞浸润分析及中药预测

目的 探寻非特异性间质性肺炎相关的关键基因、发病机制、免疫细胞浸润水平和潜在治疗中药。方法 从GEO数据库获取基因芯片GSE110147,利用R语言“limma”等相关拓展包筛选差异表达基因,通过STRING和Cytoscape软件构建蛋白质互作网络图,并筛选出关键基因。关键基因通过基因芯片GSE101286进行验证后,利用R语言“clusterProfiler”等拓展包及Cytoscape软件中的GlueGO插件进基因本体（gene ontology,GO）功能富集分析、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,再基于CIBERSORT反卷积算法分析免疫细胞浸润模式。最后将关键基因导入Coremine Medical数据库中进行相关中药预测。结果 共筛选出407个差异基因和15个关键基因。GO分析显示,非特异性间质性肺炎与剪切体、翻译过程高度相关;KEGG富集结果显示非特异性间质性肺炎与RNA剪接体通路、内质网蛋白质加工通路联系最为密切。免疫细胞浸润分析显示非特异性间质性肺炎患者组织内静息的CD4⁺记忆T细胞、嗜酸性粒细胞等浸润水平较高,而CD8⁺T细胞、浆细胞、活化NK细胞和M1巨噬细胞浸润水平较低。通过关键基因筛选到18味中药,其中雷公藤和茯苓有较大治疗潜力。结论 通过生物信息学方法,筛选非特异性间质性肺炎的关键基因,明确了潜在治疗中药,为非特异性间质性肺炎发病机制、治疗新靶点研究及新药研发提供新的方向。

Analysis of key genes and immune cell infiltration of nonspecific interstitial pneumonia and prediction of traditional Chinese medicine

Objective To explore the key genes, pathogenesis, immune cell infiltration level and potential treatment of non-specific interstitial pneumonia. Methods The gene chip GSE110147 was obtained from GEO database, and the differentially expressed genes were screened by R language "limma" and other related expansion packages. The protein interaction network map was constructed by STRING and Cytoscape software, and the key genes were screened. After the key genes were verified by gene chip GSE101286, GO function enrichment and KEGG pathway analysis were carried out by using expansion packages such as R language "clusterProfiler" and GlueGO plug-ins in Cytoscape software, and the immune cell infiltration pattern was analyzed based on CIBERSORT deconvolution algorithm. Finally, the key genes were introduced into Coremine Medical Database to predict the related traditional Chinese medicine. Results A total of 407 differential genes and 15 key genes such as HSP90AA1, EIF5B and RPS13 were screened. GO analysis showed that nonspecific interstitial pneumonia was highly correlated with shearing body and translation process, while KEGG enrichment showed that nonspecific interstitial pneumonia was most closely related to RNA splice body pathway and endoplasmic reticulum protein processing pathway. Immune cell infiltration analysis showed that the infiltration levels of resting CD4⁺ memory T cells and eosinophils in patients with nonspecific interstitial pneumonia were higher, while the infiltration levels of CD8⁺T cells, plasma cells, activated NK cells and M1 macrophages were lower. Through the screening of key genes, 18 kinds of traditional Chinese medicine were screened, among which Leigongteng (Tripterygium wilfordii Hook. f.) and FulingPoria cocos (Schw.) Wolf] have great therapeutic potential. Conclusion This study screened the key genes of non-specific interstitial pneumonia through bioinformatics methods, identified the potential treatment of traditional Chinese medicine, and provided a new direction for the pathogenesis of non-specific interstitial pneumonia, new treatment targets and new drug research and development.