Циркулирующие ДНК-маркеры при мониторинге рака лёгкого: анализ статуса метилирования ретроэлементов LINE-1

Abstract

It is known that the violation of DNA methylation processes is one of the earliest and most common events in malignant tumors. The purpose of this study was to perform a comparative analysis of the methylation level of LINE-1 retroelements in blood cirDNA in patients with lung cancer before treatment and at the stages of dynamic observation after antitumor therapy. The study included 16 patients with non-small cell lung cancer (NSCLC). The material for the study was venous blood, which was taken before the treatment (10-15 days before the start of treatment), 15-30 days after the end of the last course of non-adjuvant chemotherapy and in the postoperative period for 10-15 days. Analysis of the methylation level of LINE-1 element was performed using a quantitative methyl specific PCR .A linear increase in the methylation index of the LINE-1 fragment in response to antitumor therapy was revealed: after chemotherapy, a statistically significant increase in the methylation index was approximately 2-fold (p = 0.04, paired t-test), 1.4 times after operation indicators after chemotherapy (p = 0.134, paired t-test). As a result, after combined treatment, the LINE-1 methylation index in cc-cirDNA increased 3-fold compared to the level before treatment (p = 0.03, paired t-test). The obtained results indicate the prospectivity of the study on extended samples of lung cancer patients with the significance of the LINE-1 methylation index in blood cirDNA for predicting tumor response to treatment, evaluating the effectiveness of therapy and early detection of relapses.