Mining the key genes for ventilator-induced lung injury using co-expression network analysis

Biosci Rep. 2021 Mar 26;41(3):BSR20203235. doi: 10.1042/BSR20203235.

Abstract

Mechanical ventilation is extensively adopted in general anesthesia and respiratory failure management, but it can also induce ventilator-induced lung injury (VILI). Therefore, it is of great urgency to explore the mechanisms involved in the VILI pathogenesis, which might contribute to its future prevention and treatment. Four microarray datasets from the GEO database were selected in our investigation, and were subjected to the Weighted Gene Co-Expression Network Analysis (WGCNA) to identify the VILI-correlated gene modules. The limma package in R software was used to identify the differentially expressed genes (DEGs) between the VILI and control groups. WGCNA was constructed by merging the GSE9314, GSE9368, GSE11434 and GSE11662 datasets. A total of 49 co-expression network modules were determined as associated with VILI. The intersected genes between hub genes screened from DEGs for VILI and those identified using WGCNA were as follows: Tlr2, Hmox1, Serpine1, Mmp9, Il6, Il1b, Ptgs2, Fos and Atf3, which were determined to be key genes for VILI. Those key genes were validated by GSE86229 and quantitative PCR (qPCR) experiment to have significantly statistical difference in their expression between the VILI and control groups. In a nutshell, nine key genes with expression differences in VILI were screened by WGCNA by integrating multiple datasets.

Keywords: Bioinformatics; VILI; WGCNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 3 / genetics
  • Activating Transcription Factor 3 / metabolism
  • Animals
  • Computational Biology
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Gene Regulatory Networks*
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Activator Inhibitor 1 / metabolism
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism
  • Transcriptome*
  • Ventilator-Induced Lung Injury / genetics*
  • Ventilator-Induced Lung Injury / metabolism

Substances

  • Activating Transcription Factor 3
  • Atf3 protein, mouse
  • Interleukins
  • Membrane Proteins
  • Plasminogen Activator Inhibitor 1
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse