DNA breaks and repair in lymphocytes as a diagnostic marker in patients with gastric cancer

Abstract

Relevance: Timely detection of foci of double-strand DNA breaks with subsequent initiation of the repair mechanism plays a crucial role in the overall response to DNA damage. Untimely resolution of double-strand DNA breaks and disruptions in the repair pathway constitute a fundamental mechanism in cancer development and progression. A search for biomarkers is needed to identify foci of double-strand DNA breaks and achieve a better outcome of targeted therapy.

The study aimed to identify comparative differences in double-strand breaks and DNA repair activity in γ-H2AX and 53BP1 parameters in conditionally healthy individuals and patients with gastric cancer.

Methods: Analysis of focal points of γ-H2AX, 53BP1 with lymphocyte parameters using the automated AKLIDES® system in gastric cancer patients (n=30) and conditionally healthy individuals (n=30).

Results: Statistically significant differences were found between conditionally healthy individuals and patients with gastric cancer in γ-H2AX parameters: ‘Total number of breaks’ (p=0.001), ‘Number of nuclei with break foci’ (p=0.015), ‘Average number of breaks per cell’ (p=0.016), ‘Mean value of all break foci per cell’ (p=0.001), and in 53BP1 parameters: ‘Number of nuclei with repair foci’ (p=0.001), ‘Mean intensity of repair fluorescence in arbitrary units’ (p=0.001), ‘Mean number of repairs per cell’ (p=0.001), and ‘Damaged cells with low fluorescence intensity’ (p=0.019).

Conclusion: Biomarkers of double-strand DNA breaks with repair activity (γ-H2AX, 53BP1) have clinical significance, contributing to the development of targeted medicine in oncology.