Сirculating DNA markers for assessing antitumor therapy efficacy and monitoring metastatic colorectal cancer

Vollständiger Abstract

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Introduction: Colorectal cancer remains one of the leading causes of oncological morbidity and mortality. Aberrant methylation patterns of tumor-suppressor genes and oncogenes have been detected in circulating DNA isolated from the blood of cancer patients, suggesting their potential utility as diagnostic and prognostic markers. Objective: To evaluate changes in the methylation levels of VIM, SEPTIN9, and DCC genes in cell-surface-bound cell-free DNA (csb-cfDNA) from the blood of metastatic colorectal cancer (mCRC) patients after antitumor treatment over a long-term follow-up period. Methods: Blood samples were collected from mCRC patients (n = 21) at baseline, after three courses of preoperative chemotherapy (FOLFOXIRI regimen), 10–15 days post-surgery, and every three months during follow-up. The methylation levels of VIM, SEPTIN9, and DCC genes were quantified by methylation-specific polymerase chain reaction. Results: Preoperative chemotherapy and tumor resection were each associated with a significant decrease in SEPTIN9 and VIM methylation levels in csb-cfDNA compared to baseline (2.3-fold and 2.0-fold, respectively; p ≤ 0.05). DCC methylation decreased 1.5-fold after surgery relative to pre-treatment levels (p ≤ 0.05). During follow-up after completion of combined treatment, methylation levels of SEPTIN9, VIM, and DCC remained stable in mCRC patients without signs of disease progression (n = 8), showing no significant change from post-surgical values (days 10–15). In contrast, mCRC patients with disease progression (n = 13) exhibited increased methylation levels of SEPTIN9, VIM and DCC compared to post-resection values. Conclusion: These findings indicate that monitoring VIM, DCC, and SEPTIN9 methylation levels in csb-cfDNA has potential for evaluating the effectiveness of antitumor therapy and for early detection of relapses in mCRC patients during the follow-up period.