THE ROLE OF ABERRANT METHYLATED IN GENES APC, RASSF1A AND ITGA4 FOR DIAGNOSIS OF COLORECTAL CANCER

Autor: D S Khodyrev, Olga Brovkina, M. Gordiev, A. N. Toropovskiy, Au Vyacheslavovich Nikitin, A V Averyanov
Jazyk: ruština
Rok vydání: 2017
Předmět:
Zdroj: Клиническая практика, Vol 8, Iss 4, Pp 8-14 (2017)
ISSN: 2618-8627
2220-3095
Popis: The “gold standard” of diagnosis of colorectal cancer (CRC) is a colonoscopy. Despite the high reliability, this method is not applicable in large-scale population screening or in estimation of the disease dynamics in a particular patient. In this study, we conducted an investigation of aberrant methylation in the APC, RASSF1A and ITGA4 genes. The study included 150 pairs of tumor tissue samples with known mutation status of the RAS family genes and the surrounding histologically unchanged tissue of patients with rectal adenocarcinoma treated at the Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of Tatarstan. The methylation profiles were studied using MethyLight PCR. The most difference in the methylation between tumor and healthy tissue was observed for the ITGA4 gene (sensitivity 78%, specificity 92.7%). For the APC gene sensitivity was 32%, specificity -93.3%, for the RASSF1 gene sensitivity was 85.3%, specificity - 56.7%. Previous data on the aberrant methylation of the SEPT9 and VIM genes and new data on the APC, RASSF1A and ITGA4 genes were compared with the mutations status in the KRAS and NRAS genes. The DNA of tumor samples was significantly more often methylated in the SEPT9 (P= 0.0018) and ITGA4 (P = 0.0044) genes in the group of patients carrying mutations in the KRAS or NRAS genes, in contrast to the DNA of tumor samples of non-carriers. In statistical analysis of the effectiveness of the diagnostic test system, it was shown that our model, which includes five methylation markers (APC, RASSF1A, ITGA4, SEPT9 and VIM), has the best sensitivity and specificity (82.7% and 97.3%, respectively). The obtained model of the diagnostic test system is proposed to be used for diagnostic problems.
Databáze: OpenAIRE