Comparative Analysis of Gene Expression Profile in Tumor and Healthy Tissue in Patients with Colorectal Cancer

Abstract

INTRODUCTION: Colorectal cancer (CRC) is a sure leader among malignant neoplasms (12.3%), without taking into account gender. Five-year survival rate in stage I CRC is 91%, in stage IV 14%. The currently existing treatment methods are helpless to significantly reduce mortality the approaches should be personalized and include the use of molecular genetic methods. AIM: To perform a comparative evaluation of expression profile of samples of tumor and healthy colon tissue in CRC. MATERIALS AND METHODS: The material for the study was 19 samples of tumor tissue taken from the pathologically altered colonic mucosa of 19 patients with CRC, and 7 samples of healthy tissue taken 10 cm12 cm distally or proximally from the visual boundary of the tumor. Biopsy materials were homogenized using a mechanical method. The quality and quantity of ribonucleic acid in the eluted solution were evaluated using IMPLEN nanospectrophotometer (Germany). Gene expression was evaluated using microchip kit SurePrint G3 HumanGeneExpv3 ArrayKit (Agilent, USА). Microchips were scanned on InnoScan 1100 AL apparatus (США) with subsequent image processing in Mapix Software program (USA). RESULTS: The analysis of expression profile demonstrated 505 differentially expressed genes, 337 of which showed reduced expression and 168 enhanced expression in the tumor material. The highest expression was demonstrated by genes bound with miRNA: hsa-miR-29b-3p and hsa-miR-1-5p, and also genes Н19, FOXQ1, INHBA, MMP1, CDH3, CXCL2, MDFI, THBS2. On the contrary, genes TMIGD1, GUCA2B, ZG16, AQP8, SLC4A4, CDKN2B-AS1, CA4, СА1 demonstrated a low expression in the tumor material. Expression of genes responsible for functioning of signal pathways: IL-17, NF-kappa B, TNF, was increased in tumor samples. Genes responsible for signal pathways Fatty acid degradation, Drug metabolism cytochrome P450, Metabolic pathways, Fatty acid metabolism and Steroid hormone biosynthesis, showed reduced expression. CONCLUSION: Significant differences were found in the expression profile of tumor and healthy tissue in patients with CRC. A comparative analysis of gene enrichment and the data of the international databases permitted to identify a number of terms, genes, clusters that can be used in future in search for predictors of prognosis and of response to treatment.