Prediction and analysis of genetic effect in idiopathic pulmonary fibrosis and gastroesophageal reflux disease

IET Syst Biol. 2023 Dec;17(6):352-365. doi: 10.1049/syb2.12081. Epub 2023 Oct 31.

Abstract

With increasing research on idiopathic pulmonary fibrosis (IPF) and gastroesophageal reflux disease (GERD), more and more studies have indicated that GERD is associated with IPF, but the underlying pathological mechanisms remain unclear. The aim of the present study is to identify and analyse the differentially expressed genes (DEGs) between IPF and GERD and explore the relevant molecular mechanisms via bioinformatics analysis. Four GEO datasets (GSE24206, GSE53845, GSE26886, and GSE39491) were downloaded from the GEO database, and DEGs between IPF and GERD were identified with the online tool GEO2R. Subsequently, a series of bioinformatics analyses are conducted, including Kyoto Encyclopaedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses, the PPI network, biological characteristics, TF-gene interactions, TF-miRNA coregulatory networks, and the prediction of drug molecules. Totally, 71 genes were identified as DEGs in IPF and GERD. Five KEGG pathways, including Amoebiasis, Protein digestion and absorption, Relaxin signalling pathway, AGE-RAGE signalling pathway in diabetic complications, and Drug metabolism - cytochrome P450, were significantly enriched. In addition, eight hub genes, including POSTN, MMP1, COL3A1, COL1A2, CXCL12, TIMP3, VCAM1, and COL1A1 were selected from the PPI network by Cytoscape software. Then, five hub genes (MMP1, POSTN, COL3A1, COL1A2, and COL1A1) with high diagnostic values for IPF and GERD were validated by GEO datasets. Finally, TF-gene and miRNA interaction was identified with hub genes and predicted drug molecules for the IPF and GERD. And the results suggest that cetirizine, luteolin, and pempidine may have great potential therapeutic value in IPF and GERD. This study will provide novel strategies for the identification of potential biomarkers and valuable therapeutic targets for IPF and GERD.

Keywords: bioinformatics; data analysis; data mining; statistical analysis.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Computational Biology / methods
  • Gastroesophageal Reflux* / diagnosis
  • Gastroesophageal Reflux* / genetics
  • Gene Expression Profiling / methods
  • Humans
  • Idiopathic Pulmonary Fibrosis* / genetics
  • Matrix Metalloproteinase 1 / genetics
  • MicroRNAs* / genetics

Substances

  • Matrix Metalloproteinase 1
  • Biomarkers, Tumor
  • MicroRNAs