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. 2024 Jul 2;19(10):877-888.
doi: 10.2217/fmb-2023-0237. Epub 2024 May 3.

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

Qihuang Chen  1 , Jin Li  1
Affiliations

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

Qihuang Chen et al. Future Microbiol. .

Abstract

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.

Keywords: cystic fibrosis; gene expression omnibus; infection; nontuberculous mycobacteria; transcription factors.

Plain language summary

[Box: see text].

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Conflict of interest statement

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Selection and analysis of genes related to CF and NTM infection. (A & B) Volcano plots of differentially expressed genes in GSE154802 (A) and GSE103852 (B). (C & D) Upregulated (C) and downregulated (D) differentially expressed genes. (E & F) Shared differentially expressed genes in GO (E) and KEGG (F) enrichment analyses.
Figure 2.
Figure 2.
Construction of the PPI network and identification of hub genes in CF with NTM infection. (A) PPI network. (B) Upset plot of hub genes. EPC: Expectation Propagation Clustering; MCC: Matthews Correlation Coefficient,; MNC: Mobile Network Code
Figure 3.
Figure 3.
Functional analysis and co-expression network construction of hub genes. (A) GO and (B) KEGG enrichment analyses of hub genes. (C) Hub genes and their co-expressed genes.
Figure 4.
Figure 4.
Prediction of drugs targeting the hub genes. Expression levels of hub genes in (A) the GSE154802 dataset and (B) GSE103852 dataset. (C) Drugs targeting the hub genes PIK3R1, CXCR4 and IL1A.
Figure 5.
Figure 5.
Prediction of TFs. (A) Regulatory network of TFs, with TFs in red and hub genes in blue. (B) Significantly higher expression of KLF2, MYC, ZBTB16 and ETS1 in CF patients. (C) Lower expression of CREB1, FOXO1, YBX1 and DNMT1 in NTM-infected patients.
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