Integrated analysis of DNA methylation and gene expression profiles identified S100A9 as a potential biomarker in ulcerative colitis.
Integrated analysis of DNA methylation and gene expression profiles identified S100A9 as a potential biomarker in ulcerative colitis.
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DNA甲基化和基因表达谱的综合分析将S100A9鉴定为溃疡性结肠炎的潜在生物标志物。
DOI：
10.1042/bsr20202384
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发表时间：
2020-12-23
影响因子：
4
通讯作者：
Guo H
中科院分区：
文献类型：
--
作者：
Su S;Kong W;Zhang J;Wang X;Guo H
溃疡性结肠炎(UC)是一种常见的复发缓解型炎症性肠病，其发病机制尚不清楚。在本研究中，三名在中医院接受治疗的UC患者和三名健康对照的结肠活检样本。采用Agilent基因表达芯片对样本进行全基因组mRNA和LncRNA表达谱分析。此外，还从GEO下载了正常和UC结肠组织的全基因组DNA甲基化数据集，用于协作分析。用LIMMA BioConductor软件分析UC组织中lncRNA(Dels)和mRNAs(Dem)的差异表达。用t检验比较启动子上CpG基因的平均甲基化水平，得到UC患者与对照组的差异甲基化启动子(DMP)。用David进行功能富集化分析。将字符串数据库应用于基因功能互作网络的构建。结果，在UC样本中筛选出与补体和凝血级联、破骨细胞分化疫苗和出血性疾病密切相关的2090个DEM和1242个DELs。共保留90个DEM和72个Del用于构建功能网络，其相应基因的启动子被鉴定为DMPs。S100A9、HECW2、SOD3和HIX0114733在功能网络中的相互作用程度较高，qRT-PCR证实S100A9在UC患者结肠组织中的表达显著高于对照组，这与基因芯片分析结果一致。提示S100A9有可能作为UC的预测标志物。
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.