title: Gene signature distinguishes patients with chronic ulcerative colitis harboring remote neoplastic lesions.
abstract: 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.
authors: Section of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago, Illinois, USA. jpekow@medicine.bsd.uchicago.edu
authors: Joel
authors: J
authors: Pekow
authors: Urszula
authors: U
authors: Dougherty
authors: Yong
authors: Y
authors: Huang
authors: Edward
authors: E
authors: Gometz
authors: Jeff
authors: J
authors: Nathanson
authors: Greg
authors: G
authors: Cohen
authors: Shawn
authors: S
authors: Levy
authors: Masha
authors: M
authors: Kocherginsky
authors: Nanda
authors: N
authors: Venu
authors: Maria
authors: M
authors: Westerhoff
authors: John
authors: J
authors: Hart
authors: Amy E
authors: AE
authors: Noffsinger
authors: Stephen B
authors: SB
authors: Hanauer
authors: Roger D
authors: RD
authors: Hurst
authors: Alessandro
authors: A
authors: Fichera
authors: Loren J
authors: LJ
authors: Joseph
authors: Qiang
authors: Q
authors: Liu
authors: Marc
authors: M
authors: Bissonnette
mesh_terms: D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000150:complications*; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D003430:Cross-Sectional Studies; D018076:DNA, Complementary; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D018076:DNA, Complementary; D005819:Genetic Markers
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