Biomarkers of ulcerative colitis disease activity CXCL1, CYP2R1, LPCAT1, and NEU4 and their relationship to immune infiltrates

Sci Rep. 2023 Jul 26;13(1):12126. doi: 10.1038/s41598-023-39012-w.

Abstract

The diagnosis and assessment of ulcerative colitis (UC) poses significant challenges, which may result in inadequate treatment and a poor prognosis for patients. This study aims to identify potential activity biomarkers for UC and investigate the role of infiltrating immune cells in the disease. To perform gene set enrichment analysis, we utilized the cluster profiler and ggplot2 packages. Kyoto encyclopedia of genes and genomes was used to analyze degenerate enrichment genes. Significant gene set enrichment was determined using the cluster profiler and ggplot2 packages. Additionally, quantitative PCR (qRT-PCR) was employed to validate the expression of each marker in the ulcerative colitis model. We identified 651 differentially expressed genes (DEGs) and further investigated potential UC activity biomarkers. Our analysis revealed that CXCL1 (AUC = 0.710), CYP2R1 (AUC = 0.863), LPCAT1 (AUC = 0.783), and NEU4 (AUC = 0.833) were promising activity markers for the diagnosis of UC. Using rat DSS model, we validated these markers through qRT-PCR, which showed statistically significant differences between UC and normal colon mucosa. Infiltrating immune cell analysis indicated that M1 macrophages, M2 macrophages, activated dendritic cells (DCs), and neutrophils played crucial roles in the occurrence and progression of UC. Moreover, the activity markers exhibited varying degrees of correlation with activated memory CD4 T cells, M0 macrophages, T follicular helper cells, memory B cells, and activated DCs. The potential diagnostic genes for UC activity, such as CXCL1, CYP2R1, LPCAT1, and NEU4, as well as the infiltration of immune cells, may contribute to the pathogenesis and progression of UC.

MeSH terms

  • Animals
  • Biomarkers
  • Colitis, Ulcerative* / diagnosis
  • Colitis, Ulcerative* / genetics
  • Humans
  • Intestinal Mucosa / metabolism
  • Rats

Substances

  • Biomarkers
  • CXCL1 protein, human
  • CYP2R1 protein, human
  • Lpcat1 protein, human
  • NEU4 protein, human