Ulcerative colitis is a kind of common chronic inflammatory disease of colon, its cause is complicated, various kinds of internal and external factors participate in its pathogenesis[6]. There are currently no reliable markers for diagnosis, therefore, there is an urgent need for effective detection biomarkers. Herein, 12 DEGs were selected from three GEO datasets, consisting of 10 upregulated genes and 2 downregulated genes. Abnormal expression of 12 genes was mainly enriched during inflammation processes, including humoral immune response, response to chemokine, CXCR chemokine receptor binding. Based on the KEGG analysis, the main signaling pathway might focus on IL − 17 signaling pathway. subsequently, we identified 6 hub genes with high degrees in the PPI network. Following combined with our microarray data, CXCL8, DMBT1, REG3A, S100A8, DUOX2, and MMP1 could be useful diagnostic markers of UC.
According to the results of GO analyses, biological functions associated with UC pathogenesis included inflammatory response, zymogen granule, and chemotaxis, suggesting that the pathogenesis of UC could be facilitated by several factors, such as genetics, environment, as well as dysregulated immune responses. Based on the KEGG pathway analysis, one of the signaling pathway was enriched in the IL − 17 pathway. Several clinical trials suggest that the IL-23/IL-17 pathway might play a vital function in chronic inflammation, like ulcerative colitis and Crohn's disease.[7–9] Studies that involved mouse colitis models demonstrated that IL-17A might play a crucial function in protecting the integrity of the barrier of the intestinal epithelium, in spite of its potent proinflammatory properties[10, 11]. As such, we speculate that the IL-17 pathway could play a vital function in UC pathogenesis.
Out of the identified hub genes, CXCL8 was underscored as the gene with the highest degree of connectivity. CXCL8 ranked the first in the core gene. Based on the above analysis results, we hypothesized that CXCL8 might play an essential function in UC progression and its malignant complications. CXCL8, also known as neutrophil factor, is a member of the CXC chemokine family, which is an important mediator of inflammatory response, Increased expression of CXCL8 has been characterized in endothelial cells, cancer cells, and tumor-associated macrophages, indicating that CXCL8 may function as a significant regulatory factor within the tumor microenvironment[12]. IL‑8 is vital in the induction of colonic inflammation and has been implicated in the IBD disease activity[13]. The previous studies showed that in UC patients, CXCL8 was particularly upregulated in the inflamed mucosa, relative to the non-inflamed mucosa [14–16].The gene Deleted in Malignant Brain Tumors 1 (DMBT1), which is found in chromosome 10q25.3-q26.1, is regarded as a tumor suppressor because of its homologous deletions and downregulation in lung cancer, medulloblastoma, gastrointestinal cancers, and glioblastoma multiforme[17, 18] The existing researches have confirmed the relationship between DMBT1 and UC. Treatment with IL-22 promoted DMBT1 expression by inducing the phosphorylation of STAT3 tyrosine, as well as activation of NF-κB, suggesting the IL-22/DMBT1 axis might play a vital function in UC pathophysiology[19]. The NOX/DUOX superfamily comprises dual oxidase 1 and 2 (DUOX1 and DUOX2), NOX1, 2, 3, 4 and 5, [20]. One of the major functions of DUOX is to maintain mucosal homeostasis[21]. Several NOX family members, such as DUOX2 and NOX1 are expressed in intestinal epithelial cells and are believed to be essential factors in the host mucosal surface defence[22].Evidence indicates that DUOX2 is upregulated in inflamed tissue, and play a vital role in facilitating the progression of IBDs.[23] The REG gene family comprises four important members: REG1A, REG1B, REG3A, and REG4, all of which are expressed in the small intestine and pancreas, but only REG4 is expressed constitutively in colon epithelia [24]. Previous studies have reported that REG3A is upregulated during IBD-related colon inflammation [25, 26]. Matrix Metalloproteinase-1 (MMP-1) is vital in the degradation and remodeling of extracellular matrix, MMP-1 is associated with acute injury of colonic mucosal tissue, formation of vessels, mucosal destruction, and initial steps of ulcer formation in UC patients[27, 28]. Enhanced generation of matrix metalloproteinases (MMPs) promotes tissue damage in IBD.[29] As an important pro-inflammatory cytokine in the S100 protein family, S100A8 is a key factor in inflammation and immunity, and it’s up regulation has been observed in IBD patients. A previous study reported a consistent and significant overexpression of S100A8 mRNA in ulcerative colitis, relative to the control [30]. Moreover, S100A8 were up-regulated in the peripheral blood leucocytes of IBD patients.[31] Therefore, We supposed that these hub genes aberrantly expressed could facilitate the occurrence of UC.and their connection and significance in UC should be explored further. Finally, we validated this hub genes in our patients cohort by microarray technique, the expression of these hub genes were remarkably enhanced in the UC patients. which further suggested its convincing value.
Collectively, we performed all-inclusive bioinformatics analysis and selected 6 hub genes highly associated with UC and verified the robustness of their diagnostic significance. Meanwhile, all of them were preliminarily confirmed on our patients cohort and may act as possible biomarkers of UC. Besides, we exposed many vital gene functions and pathways that could boost our knowledge of the pathogenesis of UC. However, there is a need to conduct further studies to elucidate the precise mechanisms of UC.