title: Inflammation, adenoma and cancer: objective classification of colon biopsy specimens with gene expression signature.
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 collagenIValpha1, 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.
authors.affiliation: 2nd Department of Medicine, Semmelweis University, Budapest, Hungary. orsg1@yahoo.com
authors.forename: Orsolya
authors.initials: O
authors.lastname: Galamb
authors.forename: Balázs
authors.initials: B
authors.lastname: Györffy
authors.forename: Ferenc
authors.initials: F
authors.lastname: Sipos
authors.forename: Sándor
authors.initials: S
authors.lastname: Spisák
authors.forename: Anna Mária
authors.initials: AM
authors.lastname: Németh
authors.forename: Pál
authors.initials: P
authors.lastname: Miheller
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Tulassay
authors.forename: Elek
authors.initials: E
authors.lastname: Dinya
authors.forename: Béla
authors.initials: B
authors.lastname: Molnár
mesh_terms: D000236:Adenoma / Q000473:pathology*; D000328:Adult; D000368:Aged; D001706:Biopsy; D016000:Cluster Analysis; D003110:Colonic Neoplasms / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007249:Inflammation; D015212:Inflammatory Bowel Diseases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D000090063:Proto-Oncogene Mas