Abstract
Abnormal immune cell infiltration is associated with the pathogenesis of Crohn’s disease (CD). This study aimed to determine the diagnostic and predictive value of immune-related genes in CD. Seven Gene Expression Omnibus datasets that analyzed the gene expression in CD tissues were downloaded. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate the infiltration of the immune cells in CD tissues. Immune-related genes were screened by overlapping the immune-related genes with differentially expressed genes (DEGs). The protein-protein interaction (PPI) network was used to identify key immune-related DEGs. Diagnostic value of CD and predictive value of anti-TNFα therapy were analyzed. Immunohistochemical (IHC) assay was used to verify gene expression in CD tissues. There were significant differences among CD tissues, paired CD tissues, and normal intestinal tissues regarding the infiltration of immune cells. AQP9, CD27, and HVCN1 were identified as the key genes of the three sub-clusters in the PPI network. AQP9, CD27, and HVCN1 had mild to moderate diagnostic value in CD, and the diagnostic value of AQP9 was better than that of CD27 and HVCN1. AQP9 expression was decreased in CD after patients underwent anti-TNFα therapy, but no obvious changes were observed in non-responders. AQP9 had a moderate predictive value in patients who had undergone treatment. IHC assay confirmed that the expression of AQP9, CD27, and HVCN1 in CD tissues was higher than that in normal intestinal tissues, and AQP9, CD27 was correlated with the activity of CD. Immune-related genes, AQP9, CD27, and HVCN1 may act as auxiliary diagnostic indicators for CD, and AQP9 could serve as a promising predictive indicator in patients who underwent anti-TNF therapy.
Highlights
Crohn’s disease (CD) is a major type of inflammatory bowel disease (IBD), affecting approximately 0.5% of the worldwide population, and the incidence rate is increasing in China [1, 2]
Using Single-sample gene set enrichment analysis (ssGSEA), we revealed the landscape of infiltration of 28 immune cell subpopulations in CD by analyzing the GSE95095 dataset
Using the ANOVA method, we found that the fraction of 15/28 immune cells varied distinctly among these three kinds of tissues, and when comparing the CD tissues with non-inflammatory tissues, 22 out of 28 immune cells showed remarkable differences (Suplementary Figure S1)
Summary
Crohn’s disease (CD) is a major type of inflammatory bowel disease (IBD), affecting approximately 0.5% of the worldwide population, and the incidence rate is increasing in China [1, 2]. No curative medical approach is available for CD [5]; exploring the role of immune cells and the related cytokines is crucial for the development of effective therapeutic strategies for patients with CD. Previous studies have shown that abnormal changes in immune cells and their effective cytokines exaggerate immune responses in the intestinal mucosa of patients with CD. Human leukocyte antigen class II molecules, IL-1, IL-6, and IL-8, are overexpressed in the intestinal epithelial cells of patients with active CD [8]. This evidence demonstrates that chronic inflammation is induced by immune cells in patients with CD
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