Integrated analysis of DNA methylation and gene expression profiles identified S100A9 as a potential biomarker in ulcerative colitis

Biosci Rep. 2020 Dec 23;40(12):BSR20202384. doi: 10.1042/BSR20202384.

Abstract

Ulcerative colitis (UC) is a prevalent relapsing-remitting inflammatory bowel disease whose pathogenetic mechanisms remain elusive. In the present study, colonic biopsies samples from three UC patients treated in the Traditional Chinese Medicine Hospital and three healthy controls were obtained. The genome-wide mRNA and lncRNA expression of the samples were profiled through Agilent gene expression microarray. Moreover, the genome-wide DNA methylation dataset of normal and UC colon tissues was also downloaded from GEO for a collaborative analysis. Differential expression of lncRNA (DELs) and mRNAs (DEMs) in UC samples compared with healthy samples were identified by using limma Bioconductor package. Differentially methylated promoters (DMPs) in UC samples compared with controls were obtained through comparing the average methylation level of CpGs located at promoters by using t-test. Functional enrichment analysis was performed by the DAVID. STRING database was applied to the construction of gene functional interaction network. As a result, 2090 DEMs and 1242 DELs were screened out in UC samples that were closely associated with processes related to complement and coagulation cascades, osteoclast differentiation vaccinia, and hemorrhagic diseases. A total of 90 DEMs and 72 DELs were retained for the construction of functional network for the promoters of their corresponding genes were identified as DMPs. S100A9, HECW2, SOD3 and HIX0114733 showed high interaction degrees in the functional network, and expression of S100A9 was confirmed to be significantly elevated in colon tissues of UC patients compared with that of controls by qRT-PCR that was consistent with gene microarray analysis. These indicate that S100A9 could potentially be used as predictive biomarkers in UC.

Keywords: S100A9; integrated analysis; qRT-PCR; ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calgranulin B / genetics*
  • Calgranulin B / metabolism
  • Case-Control Studies
  • Colitis, Ulcerative / diagnosis
  • Colitis, Ulcerative / genetics*
  • Colitis, Ulcerative / metabolism
  • Colon / metabolism
  • Colon / pathology
  • DNA Methylation*
  • Epigenome*
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Genetic Association Studies
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Protein Interaction Maps
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptome*

Substances

  • Calgranulin B
  • Genetic Markers
  • S100A9 protein, human