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

Inflamm Bowel Dis 2013 Mar;19(3):461-70

Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, Illinois, USA.

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.

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http://dx.doi.org/10.1097/MIB.0b013e3182802bacDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836269PMC
March 2013
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References

(Supplied by CrossRef)

Ekbom et al.
N Engl J Med 1990

Eaden et al.
Gut 2001

Itzkowitz et al.
Gastroenterol Clin North Am 2006

Rutter et al.
Gastroenterology 2004

Rubin et al.
Gastroenterology 2006

van der Woude et al.
Apoptosis 2004

Xie et al.
World J Gastroenterol 2008

Svec et al.
Inflamm Bowel Dis 2010

Willenbucher et al.
Am J Pathol 1999

Burmer et al.
Gastroenterology 1992

Brentnall et al.
Gastroenterology 1994

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