RGD Reference Report - Gene signature distinguishes patients with chronic ulcerative colitis harboring remote neoplastic lesions. - Rat Genome Database

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Gene signature distinguishes patients with chronic ulcerative colitis harboring remote neoplastic lesions.

Authors: Pekow, Joel  Dougherty, Urszula  Huang, Yong  Gometz, Edward  Nathanson, Jeff  Cohen, Greg  Levy, Shawn  Kocherginsky, Masha  Venu, Nanda  Westerhoff, Maria  Hart, John  Noffsinger, Amy E  Hanauer, Stephen B  Hurst, Roger D  Fichera, Alessandro  Joseph, Loren J  Liu, Qiang  Bissonnette, Marc 
Citation: Pekow J, etal., Inflamm Bowel Dis. 2013 Mar;19(3):461-70. doi: 10.1097/MIB.0b013e3182802bac.
RGD ID: 153323294
Pubmed: PMID:23388545   (View Abstract at PubMed)
PMCID: PMC3836269   (View Article at PubMed Central)
DOI: DOI:10.1097/MIB.0b013e3182802bac   (Journal Full-text)


BACKGROUND: Individuals with ulcerative colitis (UC) are at increased risk for colorectal cancer. The standard method of surveillance for neoplasia in UC by colonoscopy is invasive and can miss flat lesions. We sought to identify a gene expression signature in nondysplastic mucosa without active inflammation that could serve as a marker for remote neoplastic lesions.
METHODS: Gene expression was analyzed by complementary DNA microarray in 5 normal controls, 4 UC patients without dysplasia, and 11 UC patients harboring remote neoplasia. Common gene ontology pathways of significantly differentially expressed genes were identified. Expression of genes which were progressively and significantly upregulated from controls to UC without neoplasia, to UC with remote neoplasia were evaluated by real-time polymerase chain reaction. Several gene products were also examined by immunohistochemistry.
RESULTS: Four hundred and sixty-eight genes were significantly upregulated, and 541 genes were significantly downregulated in UC patients with neoplasia compared with UC patients without neoplasia. Nine genes (ACSL1, BIRC3, CLC, CREM, ELTD1, FGG, S100A9, THBD, and TPD52L1) were progressively and significantly upregulated from controls to nondysplastic UC to UC with neoplasia. Immunostaining of proteins revealed increased expression of S100A9 and REG1α in UC-associated cancer and in nondysplastic tissue from UC patients harboring remote neoplasia compared with UC patients without neoplasia and controls.
CONCLUSIONS: Gene expression changes occurring as a field effect in the distal colon of patients with chronic UC identify patients harboring remote neoplastic lesions. These markers may lead to a more accurate and less invasive method of detection of neoplasia in patients with inflammatory bowel disease.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BIRC3HumanColitis-Associated Neoplasms disease_progressionIEP mRNA:increased expression:colonic mucosa (human)RGD 
Birc3RatColitis-Associated Neoplasms disease_progressionISOBIRC3 (Homo sapiens)mRNA:increased expression:colonic mucosa (human)RGD 
Birc3MouseColitis-Associated Neoplasms disease_progressionISOBIRC3 (Homo sapiens)mRNA:increased expression:colonic mucosa (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Birc3  (baculoviral IAP repeat-containing 3)

Genes (Mus musculus)
Birc3  (baculoviral IAP repeat-containing 3)

Genes (Homo sapiens)
BIRC3  (baculoviral IAP repeat containing 3)


Additional Information