Description

Cystic fibrosis (CF) is a genetic disease affecting multiple organs caused by mutations in the epithelial chloride channel-cystic fibrosis transmembrane conductance regulator (CFTR). A study is being conducted to identify potential genes contributing to CF progression and prognosis. The present study examined upregulated and downregulated genes in cystic fibrosis based on three microarray gene expression datasets (GSE70442, GSE2395, and GSE10406). Functional enrichment and pathway analysis were conducted for DEGs revealed their involvement in IL-17 signaling pathway, Mineral absorption, Gastric acid secretion pathways. The hub genes (MYC, EZR, S100A9, S100A8, TF, TIA1, KYNU, KLF6, CSTA, and LRRFIP1) related to this disease was identified from a constructed protein-protein interaction network. Hub genes were further analyzed for their interactions with transcription factors and miRNAs. To conclude, identifying the above hub genes may contribute to a better understanding cystic fibrosis pathophysiology.

The functional analysis must be conducted for a computational study to be physiologically relevant. Cystic fibrosis is a severe monogenic disease that affects around 7400 patients in France. More than 2100 mutations in the cystic fibrosis conductance trans membrane regulator (CFTR), the gene encoding for an epithelial ion channel that normally transports chloride and bicarbonate, lead to mucus dehydration and impaired bronchial clearance. Systematic neonatal screening in France since 2002 has enabled early diagnosis of cystic fibrosis. Although highly demanding, supportive treatments including daily chest physiotherapy, inhaled aerosol therapy, frequent antibiotic courses, nutritional and pancreatic extracts have improved the prognosis. Median age at death is now beyond 30 years. Ivacaftor was the first CFTR modulator found to both reduce sweat chloride concentration and improve pulmonary function in the rare CFTR gating mutations. Combinations of modulators such as lumacaftor + invocator or tezacaftor + invocator were found to improve pulmonary function both in patients homozygous for the F508del mutation characterized by the lack of CFTR protein and those heterozygous for F508del with minimal CFTR activity. The triple combination of invocator + tezacaftor + elexacaftor was recently shown to significantly improve pulmonary function and quality of life, to normalize sweat chloride concentration, and to reduce the need for antibiotic therapy in patients with at least one F508del mutation (83% in France). These impressive data, however, need to be confirmed in the long term. Nevertheless, it is encouraging to hear treated patients testify about their markedly improved quality of life and to observe that the number of lung transplants for cystic fibrosis decreased dramatically in France after 2020, despite the COVID pandemic, with no increase in deaths without lung transplant.

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With Regards
Ishitha

Journal Coordinator
Journal of Reproductive Endocrinology & Infertility