背景:溃疡性结肠炎是一种以结肠黏膜的慢性炎症为特征的疾病。克罗恩病是一种炎症性肠道疾病。GBP2、CASP1基因在溃疡性结肠炎和克罗恩病及其护理中的作用尚不清楚。方法:溃疡性结肠炎数据集GSE11223和克罗恩病数据集GSE186582配置文件...背景:溃疡性结肠炎是一种以结肠黏膜的慢性炎症为特征的疾病。克罗恩病是一种炎症性肠道疾病。GBP2、CASP1基因在溃疡性结肠炎和克罗恩病及其护理中的作用尚不清楚。方法:溃疡性结肠炎数据集GSE11223和克罗恩病数据集GSE186582配置文件是从GPL1708、GPL570生成的基因表达综合数据库(GEO)中下载的。进行差异表达基因(DEGs)的筛选,加权基因共表达网络分析(WGCNA),蛋白质–蛋白质相互作用(PPI)网络的构建与分析,功能富集分析,基因集合富集分析(GSEA),免疫浸润分析。绘制基因表达量热图。结果:鉴定出474个DEGs。根据基因本体论(GO)分析,它们主要富集在细胞因子介导的信号通路、细胞内囊泡、细胞表面、信号受体结合。京都基因和基因组百科全书(KEGG)分析结果显示,靶细胞主要富集在趋化因子信号通路、TNF信号通路、IL-17信号通路。WGCNA中的软阈值功率设置为5。获得了7个核心基因(GBP2, GBP1, GBP5, SAMD9L, CASP1, IFITM3, IFITM2)。基因表达量热图发现3个核心基因(GBP5, GBP2, CASP1)在溃疡性结肠炎样本中高表达,在正常组织样本中低表达。对于克罗恩病,GBP5基因在疾病和正常样本中都是低表达,GBP2、CASP1基因高表达。结论:GBP2和CASP1在溃疡性结肠炎和克罗恩病中高表达,可能通过细胞调节等途径在溃疡性结肠炎和克罗恩病的护理中发挥重要作用。Background: Ulcerative colitis is characterized by chronic inflammation of the colon mucosa. Crohn’s disease is an inflammatory bowel disease. The role of GBP2 and CASP1 genes in ulcerative colitis and Crohn’s disease and their care remains unclear. Methods: Ulcerative colitis dataset GSE11223 and Crohn’s disease dataset GSE186582 profiles were downloaded from the Gene Expression Omnibus (GEO) generated from GPL1708, GPL570. Differentially expressed genes (DEGs) were screened, followed by weighted gene co-expression network analysis (WGCNA), construction and analysis of protein-protein interaction (PPI) networks, functional enrichment analysis, gene set enrichment analysis (GSEA), and immune infiltration analysis. Heatmaps of gene expression were plotted. Results: 474 DEGs were identified. According to Gene Ontology (GO) analysis, they were mainly enriched in cytokine-mediated signaling pathways, intracellular vesicles, cell surface, and signal receptor binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the target cells were primarily enriched in chemokine signaling pathways, TNF signaling pathway, and IL-17 signaling pathway. The soft-thresholding power in WGCNA was set to 5. Seven core genes (GBP2, GBP1, GBP5, SAMD9L, CASP1, IFITM3, IFITM2) were obtained. The heatmap of gene expression revealed that three core genes (GBP5, GBP2, CASP1) were highly expressed in ulcerative colitis samples and lowly expressed in normal tissue samples. For Crohn’s disease, the GBP5 gene was lowly expressed in both disease and normal samples, while GBP2 and CASP1 genes were highly expressed. Conclusion: GBP2 and CASP1 are highly expressed in ulcerative colitis and Crohn’s disease, and may play an important role in the care of ulcerative colitis and Crohn’s disease through cellular regulation and other pathways.展开更多
The initiators caspase-9 （CASP9） and caspase-10 （CASPIO） are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms...The initiators caspase-9 （CASP9） and caspase-10 （CASPIO） are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer （CRC） susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms （SNPs） in CASP9 and CASPIO were chosen based on HapMap and the National Center of Biotechnology Information （NCBI） datasets and genotyped by restriction fragment length polymorphism （RFLP） assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 （odds ratio （OR）AA＋AG： 0.654, 95% confidence interval （CI）： 0.406-1.055; P=0.082）, rs4233532 （ORcc： 1.667, 95% CI： 0.967-2.876; Oacm： 1.435, 95% CI： 0.998-2.063; P=0.077）, and rs2881930 （ORcc： 0.263, 95% CI： 0.095-0.728, P=0.036） showed possible association with CRC risk. However, none of the three SNPs, rs4646077 （ORAA＋AG： 1.233, 95% CI： 0.903-1.683）, rs4233532 （ORcc： 0.892, 95% CI： 0.640-1.243; ORcT： 1.134, 95% CI： 0.897-1.433）, and rs2881930 （ORcc： 1.096, 95% CI： 0.620-1.938; ORcT： 1.009, 95% CI： 0.801-1.271）, remained significant with CRC risk in the validation set, even after stratification for different tumor locations （colon or rectum）. In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set （OR： 1.755, 95% CI： 1.319-2.334）. Our results found that polymorphisms of CASP9 and CASPIO genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC.展开更多
文摘背景:溃疡性结肠炎是一种以结肠黏膜的慢性炎症为特征的疾病。克罗恩病是一种炎症性肠道疾病。GBP2、CASP1基因在溃疡性结肠炎和克罗恩病及其护理中的作用尚不清楚。方法:溃疡性结肠炎数据集GSE11223和克罗恩病数据集GSE186582配置文件是从GPL1708、GPL570生成的基因表达综合数据库(GEO)中下载的。进行差异表达基因(DEGs)的筛选,加权基因共表达网络分析(WGCNA),蛋白质–蛋白质相互作用(PPI)网络的构建与分析,功能富集分析,基因集合富集分析(GSEA),免疫浸润分析。绘制基因表达量热图。结果:鉴定出474个DEGs。根据基因本体论(GO)分析,它们主要富集在细胞因子介导的信号通路、细胞内囊泡、细胞表面、信号受体结合。京都基因和基因组百科全书(KEGG)分析结果显示,靶细胞主要富集在趋化因子信号通路、TNF信号通路、IL-17信号通路。WGCNA中的软阈值功率设置为5。获得了7个核心基因(GBP2, GBP1, GBP5, SAMD9L, CASP1, IFITM3, IFITM2)。基因表达量热图发现3个核心基因(GBP5, GBP2, CASP1)在溃疡性结肠炎样本中高表达,在正常组织样本中低表达。对于克罗恩病,GBP5基因在疾病和正常样本中都是低表达,GBP2、CASP1基因高表达。结论:GBP2和CASP1在溃疡性结肠炎和克罗恩病中高表达,可能通过细胞调节等途径在溃疡性结肠炎和克罗恩病的护理中发挥重要作用。Background: Ulcerative colitis is characterized by chronic inflammation of the colon mucosa. Crohn’s disease is an inflammatory bowel disease. The role of GBP2 and CASP1 genes in ulcerative colitis and Crohn’s disease and their care remains unclear. Methods: Ulcerative colitis dataset GSE11223 and Crohn’s disease dataset GSE186582 profiles were downloaded from the Gene Expression Omnibus (GEO) generated from GPL1708, GPL570. Differentially expressed genes (DEGs) were screened, followed by weighted gene co-expression network analysis (WGCNA), construction and analysis of protein-protein interaction (PPI) networks, functional enrichment analysis, gene set enrichment analysis (GSEA), and immune infiltration analysis. Heatmaps of gene expression were plotted. Results: 474 DEGs were identified. According to Gene Ontology (GO) analysis, they were mainly enriched in cytokine-mediated signaling pathways, intracellular vesicles, cell surface, and signal receptor binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the target cells were primarily enriched in chemokine signaling pathways, TNF signaling pathway, and IL-17 signaling pathway. The soft-thresholding power in WGCNA was set to 5. Seven core genes (GBP2, GBP1, GBP5, SAMD9L, CASP1, IFITM3, IFITM2) were obtained. The heatmap of gene expression revealed that three core genes (GBP5, GBP2, CASP1) were highly expressed in ulcerative colitis samples and lowly expressed in normal tissue samples. For Crohn’s disease, the GBP5 gene was lowly expressed in both disease and normal samples, while GBP2 and CASP1 genes were highly expressed. Conclusion: GBP2 and CASP1 are highly expressed in ulcerative colitis and Crohn’s disease, and may play an important role in the care of ulcerative colitis and Crohn’s disease through cellular regulation and other pathways.
基金Project supported by the National Natural Science Foundation of China (No.30872177)the Specialized Research Fund for the Doctoral Program of Higher Education (No.20090101110113)
文摘The initiators caspase-9 （CASP9） and caspase-10 （CASPIO） are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer （CRC） susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms （SNPs） in CASP9 and CASPIO were chosen based on HapMap and the National Center of Biotechnology Information （NCBI） datasets and genotyped by restriction fragment length polymorphism （RFLP） assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 （odds ratio （OR）AA＋AG： 0.654, 95% confidence interval （CI）： 0.406-1.055; P=0.082）, rs4233532 （ORcc： 1.667, 95% CI： 0.967-2.876; Oacm： 1.435, 95% CI： 0.998-2.063; P=0.077）, and rs2881930 （ORcc： 0.263, 95% CI： 0.095-0.728, P=0.036） showed possible association with CRC risk. However, none of the three SNPs, rs4646077 （ORAA＋AG： 1.233, 95% CI： 0.903-1.683）, rs4233532 （ORcc： 0.892, 95% CI： 0.640-1.243; ORcT： 1.134, 95% CI： 0.897-1.433）, and rs2881930 （ORcc： 1.096, 95% CI： 0.620-1.938; ORcT： 1.009, 95% CI： 0.801-1.271）, remained significant with CRC risk in the validation set, even after stratification for different tumor locations （colon or rectum）. In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set （OR： 1.755, 95% CI： 1.319-2.334）. Our results found that polymorphisms of CASP9 and CASPIO genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC.
