Comparative study of gene expression by cDNA microarray in human colorectal cancer tissues and normal mucosa

• Published in: International journal of oncology Vol. 29; no. 1; pp. 83 - 94
• Main Authors: BIANCHINI, Michele, LEVY, Estrella, ZUCCHINI, Cinzia, PINSKI, Victor, MACAGNO, Carlos, DE SANCTIS, Paola, VALVASSORI, Luisa, CARINCI, Paolo, MORDOH, José
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01.07.2006
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Adult; Aged; Aged, 80 and over; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; beta 2-Microglobulin - genetics; beta 2-Microglobulin - metabolism; Biological and medical sciences; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - metabolism; HLA Antigens - genetics; HLA Antigens - metabolism; HLA-E Antigens; Humans; Intestinal Mucosa - metabolism; Male; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - metabolism; Middle Aged; Neuronal Apoptosis-Inhibitory Protein - genetics; Neuronal Apoptosis-Inhibitory Protein - metabolism; Oligonucleotide Array Sequence Analysis - methods; Reproducibility of Results; RNA, Messenger - analysis; RNA, Messenger - metabolism; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Human; anti-apoptotic phenotype; Rectal disease; Mucosa; Colorectal cancer; cDNA microarray; Malignant tumor; Gene expression; Gene expression profile; Colonic disease; Phenotype; Colon cancer; Cancerology; Complementary DNA; Gene; Tissue microarrays; gene expression profiles; Digestive diseases; Intestinal disease; Comparative study; Apoptosis
• DOI: 10.3892/ijo.29.1.83
• ISSN: 1019-6439

The causative molecular pathways underlying the pathogenesis of colorectal cancer (CRC) need to be better characterized. The purpose of our study was to better understand the genetic mechanism of oncogenesis for human colorectal cancer and to identify new potential tumor markers of use in clinical practice. We used cDNA microarrays to compare gene expression profiles of colorectal biopsies from 25 CRC patients and 13 normal mucosa from adjacent non-cancerous tissues. Findings were validated by real-time PCR; in addition, western blotting and immunochemistry analysis were carried out as further confirmation of differential expression at a protein level. Comparing cancerous tissues with normal colonic mucosa we identified 584 known genes differentially expressed to a significant degree (p<0.001). Many of the transcripts that were more abundant in tumors than in non-neoplastic tissues appear to reflect important events for colon carcinogenesis. For example, a significant number of these genes serve as apoptotic inhibitors (e.g. BFAR, BIRC1, BIRC6). Furthermore, we observed the simultaneous up-regulation of HLA-E and the down-regulation of beta2-microglobulin; these genes strongly support a potential tumor escape strategy from immune surveillance in colon cancer tissues. Our study provides new gene candidates in the pathogenesis of human CRC disease. From our results we hypothesize that CRC cells escape immune surveillance through a specific gene expression alteration; moreover, over-expression of several survival genes seems to confer a more anti-apoptotic phenotype. These genes are involved in pathways not previously implicated in CRC pathogenesis and they may provide new targets for therapy.