Faculty Collaboration Database

Gene signature distinguishes patients with chronic ulcerative colitis harboring remote neoplastic lesions. Inflamm Bowel Dis 2013 Mar;19(3):461-70

Date

02/08/2013

Pubmed ID

23388545

Pubmed Central ID

PMC3836269

DOI

10.1097/MIB.0b013e3182802bac

Scopus ID

2-s2.0-84876383218 (requires institutional sign-in at Scopus site)   41 Citations

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.

Author List

Pekow J, Dougherty U, Huang Y, Gometz E, Nathanson J, Cohen G, Levy S, Kocherginsky M, Venu N, Westerhoff M, Hart J, Noffsinger AE, Hanauer SB, Hurst RD, Fichera A, Joseph LJ, Liu Q, Bissonnette M

MESH terms used to index this publication - Major topics in bold

Case-Control Studies
Colitis, Ulcerative
Colon
Colorectal Neoplasms
Cross-Sectional Studies
DNA, Complementary
Down-Regulation
Female
Gene Expression Profiling
Genetic Markers
Humans
Immunohistochemistry
Intestinal Mucosa
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Real-Time Polymerase Chain Reaction
Transcriptome
Up-Regulation