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

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.

Novel biomarkers related to oxidative stress and immunity in chronic kidney disease

“…These inflammatory complexes serve as pivotal components within multi-protein oligomer structures and innate immune networks, becoming engaged in 'aseptic' inflammatory responses triggered by damage-related molecular patterns (DAMPs) [ 28 , 29 ]. Studies have elucidated that S100A9 not only displays elevated levels in inflammatory conditions like inflammatory bowel disease, systemic lupus erythematosus, and rheumatoid arthritis, but it also exhibits a close association with numerous neurodegenerative diseases of the central nervous system [ [30] , [31] , [32] , [33] ]. Within the domain of renal diseases, Yang et al [ 34 ] identified the S100a9 hi Ly6c hi IMs population as early responders in acute kidney injury (AKI).…”

Identification of immune-related hub genes contributing to the pathogenesis, diagnosis, and remission of ulcerative colitis by integrated bioinformatic analyses

“…[ 25 ] Lawrance IC et al [ 26 ] proposed the elevated expression of S100A9 in UC for the first time, which was consistent with several studies including ours. [ 27 , 28 ] Calprotectin is a unique heterodimer of S100A8 and S100A9, which are two S100 EF-hand calcium binding proteins. Mortensen JH et al [ 29 ] found out that there was an association between neutrophil activity and endoscopic severity from patients with inflammatory bowel disease and a specific calprotectin epitope in serum, CPA9-HNE.…”

Identification of hub genes and key pathways in pediatric Crohn’s disease using next generation sequencing and bioinformatics analysis

“…These autoimmune diseases responsible genes might be critical for the development of CD. Recently, study found that CXCL5 [454], S100A12 [455], OSM (oncostatin M) [456], LRG1 [457], LCN2 [458], CXCL1 [459], S100A9 [460], IFITM1 [461], XBP1 [462], MMP3 [457], IFITM3 [463], IL1B [464], GBP5 [465], HGF (hepatocyte growth factor) [466], CXCL9 [467], SLC11A1 [468], IL1RN [469], STAT1 [470], CYP27B1 [471], MMP1 [472], SOCS3 [473], TLR8 [474], CD55 [475], CCL28 [476], FCGR2A [477], CCL2 [478], CFB (complement factor B) [479], CD14 [480], GPR84 [481], PCSK9 [482], FOXP3 [483], LPL (lipoprotein lipase) [484], IL1R2 [485], TLR2 [486], MEFV (MEFV innate immuity regulator, pyrin) [487], VWF (von Willebrand factor) [488], NOD2 [489], DMBT1 [490], HSPA6 [491], TIMP1 [492], ICAM1 [493], EGR1 [494], CCL11 [495], IFNG (interferon gamma) [496], APOE (apolipoprotein E) [497] FGR (FGR proto-oncogene, Src family tyrosine kinase) [498], IL6 [499], SPP1 [192], IL11 [500], RNF186 [501], MMP2 [502], CD24 [503], SPHK1 [504], GZMB (granzyme B) [505], MUC5AC [506], SERPINA3 [507], TWIST1 [508], PLAU (plasminogen activator, urokinase) [509], CA2 [510], CA9 [510], CTLA4 [511], PADI4 [512], MMP13 [513], MPO (myeloperoxidase) [244], LEFTY1 [514], CA1 [515], MMP7 [513], ABCG2 [516], CYP2J2 [517], AICDA (activation induced cytidine deaminase) [518], CYP2D6 [519], CYP3A5 [52...…”