Integrative computational approach identifies immune‐relevant biomarkers in ulcerative colitis

Abstract

Ulcerative colitis is a common inflammatory bowel disease with a complex genetic and immune etiology. Immune infiltration plays a vital role in the development of ulcerative colitis. To explore potential biomarkers for ulcerative colitis and analyze characteristics of immune cell infiltration, we used bioinformatic analyses, including machine learning algorithms, cell type deconvolution methods, and pathway enrichment methods. In this study, we identified 216 differentially expressed mRNAs (DEMs), of which 153 were upregulated, and 63 were downregulated genes. DEMs were mainly enriched in infiltrating neutrophils and regulation of leukocyte migration. Moreover, eight candidate biomarkers, DPP10, MST1L, DPP10-AS1, CEP55, ACSL1, MGP, OLFM4, and SGK1, were identified. Of these candidate biomarkers, MST1L, OLFM4, and DPP10 were then validated in the GSE48958 dataset and were predicted to be strongly correlated with infiltrating immune cells of ulcerative colitis. The underlying mechanism of these key genes in the development of colitis was also predicted by gene set variation analysis. To further validate these biomarkers' expression in ulcerative colitis, we determined mRNA levels of SGK1, CEP55, ACSL1, OLFM4, and DPP10 in lipopolysaccharides (LPS)stimulated Raw264.7 cells by quantitative reverse transcription-polymerase chain reaction. We also examined SGK1, CEP55, ACSL1, OLFM4, DPP10, and MGP expression in the colon tissues of dextran sodium sulfate-induced colitis mice. Consistent with the predicted computational results, the mRNA levels of these candidate genes were markedly changed in LPS-stimulated Raw264.7 cells and inflamed colon tissues. Hence, our findings indicated that these critical genes may act as diagnostic biomarkers for ulcerative colitis and that differential immune infiltration cells may help illustrate the progression of ulcerative colitis.

Knockdown of TOP2A suppresses IL‐17 signaling pathway and alleviates the progression of ulcerative colitis

“…Moreover, the inhibitor of PBK can suppress the proliferation of colorectal cancer cells with PBK expression 21 . He et al screen out 10 hub genes by bioinformatics analysis, including CEP55, which may be diagnostic biomarkers for UC 22 . High expression of CEP55 has also been associated with poor prognosis of non‐small cell lung cancer, gallbladder cancer, and endometrial cancer 23–25 .…”

“… 21 He et al screen out 10 hub genes by bioinformatics analysis, including CEP55, which may be diagnostic biomarkers for UC. 22 High expression of CEP55 has also been associated with poor prognosis of non‐small cell lung cancer, gallbladder cancer, and endometrial cancer. 23 , 24 , 25 Chen et al identify 14 key genes related to the pathogenesis of colon cancer, including CEP55, TOP2A, RRM2, NCAPG2, providing new directions for elucidating the molecular mechanisms of colon cancer.…”

pDNA-tachyplesin treatment stimulates the immune system and increases the probability of apoptosis in MC4-L2 tumor cells

“…The molecular mechanism behind the suppression of tachyplesin remains unclear. To determine whether Neutrophils were converted into myeloblasts, evaluating the levels of biomarkers associated with the mTOR signaling pathways is crucial (He et al 2022 ). Interestingly, ß-element derived from the Chinese herb Curcuma wenyujin can induce the re-differentiation of myeloblasts into neutrophils.…”

Large scale phenotyping of long COVID inflammation reveals mechanistic subtypes of disease after COVID-19 hospitalisation

“…DDP10 can modulate tissue in ammation, and increased DPP10 expression is associated with Ulcerative Colitis, suggesting that GI symptoms may result from enteric, as well as systemic, in ammation. 38,39 Elevated SCG3 suggests disturbance of the brain-gut axis, as observed in patients with irritable bowel syndrome. 40 Cognitive impairment was associated with elevated Neurofascin (NFASC; OR=1.05), Spondin-1 (SPON-1; OR=1.03) and Iduronate sulfatase (IDS; OR=1.04)(Fig.…”