Inflammation, adenoma and cancer: objective classification of colon biopsy specimens with gene expression signature

Background and Aims: Gene expression analysis of colon biopsies using high-density oligonucleotide microarray can contribute to the understanding of local pathophysiological alterations and to functional classification of precancerous adenoma, different stage colorectal carcinomas (CRC) and inflammatory bowel diseases (IBD). Results: Significant overexpression of collagen IV, lipocalin-2, caveolin-1, calumenin genes, and significant dowregulation of aquaporin-8, amnionless homolog, prostaglandin D2 receptor genes were detected in CRC patients compared to normal. Adenoma samples were characterized by upregulated CD44 antigen, met proto-oncogene and downregulated chemokine ligand-12, ADAM-like decysin-1 and ATP-binding casette A8 discriminatory genes. In IBD samples significantly increased lipocalin-2, interferon induced transmembrane protein 1 and 3 mRNA levels, decreased zinc finger protein 91 and transient receptor potential cation channel M6 mRNA levels were found. Ulcerative colitis and Crohn’s disease can be distinguished according to the top five genes: cyclin-G2; tripartite motif-containing-31; TNFR shedding aminopeptidase regulator-1; C-type lectin superfamily member-14 and AMICA. 88.3-97.8% of the cases was correctly classified according to discriminatory genes. Conclusions: Our whole genomic microarray analysis of biopsy samples provides discriminative signatures, and an insight into pathophysiological background of colonic diseases. The results afford a data warehouse which can be further mined for in-depth pathway analyses. Keywords: Colon biopsy specimens in diseased and normal state Total RNA was extracted, amplified and biotinylated from frozen colonic biopsies of 15 patients with CRC, 15 with adenoma, 15 with IBD and 8 healthy normal controls. Genome-wide gene expression profile was evaluated by HGU133 Plus 2.0 microarrays. Gene expression was also measured by real-time PCR.