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Disease Markers
Volume 25 (2008), Issue 1, Pages 1-16
http://dx.doi.org/10.1155/2008/586721

Inflammation, Adenoma and Cancer: Objective Classification of Colon Biopsy Specimens with Gene Expression Signature

Orsolya Galamb,1,4 Balázs Györffy,2 Ferenc Sipos,1 Sándor Spisák,1 Anna Mária Németh,1 Pál Miheller,1 Zsolt Tulassay,1,4 Elek Dinya,3 and Béla Molnár1,4

12nd Department of Medicine, Semmelweis University, Budapest, Hungary
2Joint Research Laboratory of the Hungarian Academy of Sciences and the Semmelweis University for Pediatrics and Nephrology, 1st Department of Paediatrics, Semmelweis University Budapest, Hungary
3EGIS Pharmaceuticals Ltd. Medical Department, Budapest, Hungary
4Hungarian Academy of Science, Molecular Medicine Research Unit, Budapest, Hungary

Received 12 August 2008; Accepted 12 August 2008

Copyright © 2008 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Gene expression analysis of colon biopsies using high-density oligonucleotide microarrays can contribute to the understanding of local pathophysiological alterations and to functional classification of adenoma (15 samples), colorectal carcinomas (CRC) (15) and inflammatory bowel diseases (IBD) (14). Total RNA was extracted, amplified and biotinylated from frozen colonic biopsies. Genome-wide gene expression profile was evaluated by HGU133plus2 microarrays and verified by RT-PCR. We applied two independent methods for data normalization and used PAM for feature selection. Leave one-out stepwise discriminant analysis was performed. Top validated genes included collagenIVα1, lipocalin-2, calumenin, aquaporin-8 genes in CRC; CD44, met proto-oncogene, chemokine ligand-12, ADAM-like decysin-1 and ATP-binding casette-A8 genes in adenoma; and lipocalin-2, ubiquitin D and IFITM2 genes in IBD. Best differentiating markers between Ulcerative colitis and Crohn's disease were cyclin-G2; tripartite motif-containing-31; TNFR shedding aminopeptidase regulator-1 and AMICA. The discriminant analysis was able to classify the samples in overall 96.2% using 7 discriminatory genes (indoleamine-pyrrole-2,3-dioxygenase, ectodermal-neural cortex, TIMP3, fucosyltransferase-8, collectin sub-family member 12, carboxypeptidase D, and transglutaminase-2). Using routine biopsy samples we successfully performed whole genomic microarray analysis to identify discriminative signatures. Our results provide further insight into the pathophysiological background of colonic diseases. The results set up data warehouse which can be mined further.