Transcriptional analysis of left-sided colitis, pancolitis, and ulcerative colitis-associated dysplasia.

Bjerrum, Jacob T; Nielsen, Ole H; Riis, Lene B; Pittet, Valerie; Müller, Christoph; Rogler, Gerhard; Olsen, Jørgen (2014). Transcriptional analysis of left-sided colitis, pancolitis, and ulcerative colitis-associated dysplasia. Inflammatory bowel diseases, 20(12), pp. 2340-2352. Lippincott Williams & Wilkins 10.1097/MIB.0000000000000235

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BACKGROUND It is unknown why patients with extensive ulcerative colitis (UC) have a higher risk of colorectal cancer compared with patients with left-sided UC. This study characterizes the inflammatory processes in left-sided UC, pancolitis, and UC-associated dysplasia at the transcriptional level to identify potential biomarkers and transcripts of importance for the carcinogenic behavior of chronic inflammation. METHODS The Affymetrix GeneChip Human Genome U133 Plus 2.0 was applied on colonic biopsies from UC patients with left-sided UC, pancolitis, dysplasia, and controls. Reverse transcription polymerase chain reaction and immunohistochemistry were performed for validating selected transcripts in the initial cohort and in 2 independent cohorts of patients with UC. Microarray data were analyzed by principal component analysis, and reverse transcription polymerase chain reaction and immunohistochemistry data by the Wilcoxon's rank-sum test. RESULTS The principal component analysis results revealed separate clusters for left-sided UC, pancolitis, dysplasia, and controls. Close clustering of dysplastic and pancolitic samples indicated similarities in gene expression. Indeed, 101 and 656 parallel upregulated and downregulated transcripts, respectively, were identified in specimens from dysplasia and pancolitis. Validation of selected transcripts hereof identified insulin receptor alpha (INSRA) and MAP kinase interacting serine/threonine kinase 2 (MKNK2) with an enhanced expression in dysplasia compared with left-sided UC and controls, whereas laminin γ2 (LAMC2) was found with a lower expression in dysplasia compared with the remaining 3 groups. CONCLUSIONS This study demonstrates pancolitis and left-sided UC as distinct inflammatory processes at the transcriptional level, and identifies INSRA, MKNK2, and LAMC2 as potential critical transcripts in the inflammation-driven preneoplastic process of UC.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Müller, Christoph

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health

ISSN:

1078-0998

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Doris Haefelin

Date Deposited:

23 Feb 2015 08:28

Last Modified:

01 Jan 2016 02:30

Publisher DOI:

10.1097/MIB.0000000000000235

PubMed ID:

25358065

BORIS DOI:

10.7892/boris.63584

URI:

https://boris.unibe.ch/id/eprint/63584

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