Molecular mechanism analysis of nontuberculous mycobacteria infection in patients with cystic fibrosis

Aim: This study aims to explore the molecular mechanisms of cystic fibrosis (CF) complicated with nontuberculous mycobacteria (NTM) infection. Materials & methods: Expression profiles of CF with NTM-infected patients were downloaded from GEO database. Intersection analysis yielded 78 genes associated with CF with NTM infection. The protein–protein interaction (PPI) network and the functions of hub genes were investigated. Results: Five hub genes (PIK3R1, IL1A, CXCR4, ACTN1, PFN1) were identified, which were primarily enriched in actin-related biological processes and pathways. Transcription factors RELA, JUN, NFKB1 and FOS that regulated hub genes modulated IL1A expression, while 21 other transcription factors regulated CXCR4 expression. Conclusion: In summary, this study may provide new insights into the mechanisms of CF with NTM infection. Actin-related biological processes and pathways may play a crucial role in the process of nontuberculous mycobacteria (NTM) infection in cystic fibrosis (CF) patients. IL1A and CXCR4 may be important genes involved in the development of CF patients with comorbid NTM infection. Modulating transcription factors such as RELA, NFKB1, KLF2 and FOXO1 may be beneficial for the treatment of CF patients.研究目的：本研究旨在探讨囊性纤维化（cystic fibrosis, CF）合并非结核分枝杆菌（nontuberculous mycobacteria, NTM）感染的分子机制。 材料与方法：从基因表达综合数据库（Gene Expression Omnibus, GEO）下载CF合并NTM感染患者的表达谱（expression profiles）数据。通过交集分析得到78个与CF合并NTM感染相关的基因。进一步探究了蛋白质相互作用（protein-protein interaction, PPI）网络及核心基因（hub genes）的功能。 研究结果：共筛选出5个核心基因（PIK3R1、IL1A、CXCR4、ACTN1、PFN1），这些基因主要富集于肌动蛋白相关的生物学过程及通路。调控核心基因的转录因子（transcription factors）RELA、JUN、NFKB1及FOS可调节IL1A的表达，另有21种转录因子可调控CXCR4的表达。 研究结论：综上，本研究可为CF合并NTM感染的发病机制提供新的研究视角。肌动蛋白相关的生物学过程及通路在CF患者合并NTM感染的进程中可能发挥关键作用。IL1A与CXCR4可能是参与CF患者合并NTM感染发生发展的重要基因。调控RELA、NFKB1、KLF2及FOXO1等转录因子或可用于CF患者的临床治疗。