TY - JOUR
T1 - Transcriptional analysis of left-sided colitis, pancolitis, and ulcerative colitis-associated dysplasia
AU - Bjerrum, Jacob T
AU - Nielsen, Ole H
AU - Riis, Lene B
AU - Pittet, Valerie
AU - Mueller, Christoph
AU - Rogler, Gerhard
AU - Olsen, Jørgen
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Background: It is unknown why patients with extensive ulcerative colitis (UC) have a higher risk of colorectal cancer compared with patients with leftsided 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 g2 (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.
AB - Background: It is unknown why patients with extensive ulcerative colitis (UC) have a higher risk of colorectal cancer compared with patients with leftsided 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 g2 (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.
U2 - 10.1097/mib.0000000000000235
DO - 10.1097/mib.0000000000000235
M3 - Journal article
C2 - 25358065
SN - 1078-0998
VL - 20
SP - 2340
EP - 2352
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
IS - 12
ER -
