Dataset Information

NOD2 status and human ileal gene expression.

ABSTRACT: NOD2 single nucleotide polymorphisms have been associated with increased risk of ileal Crohn's disease (CD). This exploratory study was conducted to compare ileal mucosal gene expression in CD patients with and without NOD2 risk alleles.Ileal samples were prospectively collected from 18 nonsmoking CD patients not treated with anti-TNF-? biologics and 9 nonsmoking control patients without inflammatory bowel disease undergoing initial resection and genotyped for the 3 major NOD2 risk alleles (Arg702Trp, Gly908Arg, Leu1007fs). Microarray analysis was performed in samples from 4 NOD2(R) (at least 1 risk allele) CD patients, 4 NOD2(NR) (no risk alleles) CD patients, and 4 NOD2(NR) controls. Candidate genes selected by significance analysis of microarrays (SAM) were confirmed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays of all the samples.SAM detected upregulation of 18 genes in affected ileum in NOD2(R) compared to NOD2(NR) CD patients, including genes related to lymphocyte activation. SAM also detected altered ileal gene expression in unaffected NOD2(NR) ileal mucosal CD samples compared to NOD2(NR) control samples. qRT-PCR conducted on all the samples confirmed that increased CD3D expression in affected samples was associated with NOD2(R) status, and that increased MUC1, DUOX2, DMBT1 and decreased C4orf7 expression in unaffected samples was associated with CD, independent of NOD2 status.The results support the concept that NOD2 risk alleles contribute to impaired regulation of inflammation in the ileum. Furthermore, altered ileal gene expression, independent of NOD2 status, is detected in the unaffected proximal margin of resected ileum from CD patients.

SUBMITTER: Hamm CM

PROVIDER: S-EPMC4002261 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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NOD2 status and human ileal gene expression.

Hamm Christina M CM Reimers Melissa A MA McCullough Casey K CK Gorbe Elizabeth B EB Lu Jianyun J Gu C Charles CC Li Ellen E Dieckgraefe Brian K BK Gong Qingqing Q Stappenbeck Thaddeus S TS Stone Christian D CD Dietz David W DW Hunt Steven R SR

Inflammatory bowel diseases 20101001 10

<h4>Background</h4>NOD2 single nucleotide polymorphisms have been associated with increased risk of ileal Crohn's disease (CD). This exploratory study was conducted to compare ileal mucosal gene expression in CD patients with and without NOD2 risk alleles.<h4>Methods</h4>Ileal samples were prospectively collected from 18 nonsmoking CD patients not treated with anti-TNF-α biologics and 9 nonsmoking control patients without inflammatory bowel disease undergoing initial resection and genotyped for ...[more]

PMID: 20155851

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Project description:The occurrence of large publically available repositories of human breast tumor gene expression profiles provides an important resource to discover new breast cancer biomarkers and therapeutic targets. For example, knowledge of the expression of the estrogen and progesterone hormone receptors (ER and PR), and that of the ERBB2 in breast tumor samples enables choice of therapies for the breast cancer patients that express these proteins. Identifying new biomarkers and therapeutic agents affecting the activity of signaling pathways regulated by the hormone receptors or ERBB2 might be accelerated by knowledge of their expression levels in large gene expression profiling data sets. Unfortunately, the status of these receptors is not invariably reported in public databases of breast tumor gene expression profiles. Attempts have been made to employ a single probe set to identify ER, PR and ERBB2 status, but the specificity or sensitivity of their prediction is low. We enquired whether estimation of ER, PR and ERBB2 status of profiled tumor samples could be improved by using multiple probe sets representing these three genes and others with related expression.We used 8 independent datasets of human breast tumor samples to define gene expression signatures comprising 24, 51 and 14 genes predictive of ER, PR and ERBB2 status respectively. These signatures, as demonstrated by sensitivity and specificity measures, reliably identified hormone receptor and ERBB2 expression in breast tumors that had been previously determined using protein and DNA based assays. Our findings demonstrate that gene signatures can be identified which reliably predict the expression status of the estrogen and progesterone hormone receptors and that of ERBB2 in publically available gene expression profiles of breast tumor samples. Using these signatures to query transcript profiles of breast tumor specimens may enable discovery of new biomarkers and therapeutic targets for particular subtypes of breast cancer.

Dataset Information

NOD2 status and human ileal gene expression.

Publications

NOD2 status and human ileal gene expression.

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