DNA DAMAGE MARKERS IN THE DIAGNOSIS OF EARLY STAGE PARTHANATOSIS IN LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA

Abstract

Background. One of the mechanisms of programmed cell death involved in the development of hepatocellular carcinoma (HCC) is parthanatosis, whose sequential stages are characterized by DNA damage, the formation of 8-hydroxyguanine (OGG1), hyperactivation of poly(ADP-ribose) polymerase (PARP-1), induction of hypoxia-inducible factor 1 (HIF-1), and the release of apoptosis-inducing factor (AIF) from the mitochondria into the nucleus for caspaseindependent genome fragmentation. The resulting DNA base damage may cause mutations leading to carcinogenesis. Objective. To determine the content of markers of the initial stage of parthanatosis (OGG1, HIF-1α) in liver tissue in patients with liver cirrhosis and HCC. Material and Methods. The object of the study is liver tissue homogenates (biopsies and autopsy material). The following are presented: a comparison group with 10 homogenates of unchanged liver parenchyma from patients without both cirrhosis and HCC (group 1), patients with cirrhosis but without HCC (group 2, n=30), patients with both cirrhosis and HCC (group 3, n=30), patients with HCC but without cirrhosis (group 4, n=20). All patients were from clinics of the Grodno region, hospitalized in 2015–2025. The subject of the study is the level and diagnostic significance of the OGG1 enzyme and HIF-1α protein, determined by ELISA on a Mindray 96RA analyzer (China) in patient tissue samples using a reagent kit manufactured by Wuhan Fine Biological Technology Co. Ltd (China). Statistical processing of the results was performed in the Microsoft Excel software environment. Results. OGG1 levels significantly differed between the study groups and the comparison group (p<0.05). The average OGG1 level in groups 2, 3, and 4 increased by 7-, 11-, and 24-fold, respectively, compared to the comparison group. The highest OGG1 level was observed in group 4 among patients with HCC without cirrhosis. The mean HIF-1α level was less variable, with no difference between any of the study groups and the comparison one (p>0.05). Conclusion. Gradual increase in OGG1 activity in groups with cirrhosis, both cirrhosis and cancer, and with liver cancer presented as HCC indicates an intensification of promutagenic oxidative DNA damage resulting from various causes of liver damage. The absence of significant deviations in HIF-1α levels in cirrhosis and HCC suggests that carcinogenesis can develop at a stage of low infection activity and subtle disturbances in cellular metabolism. OGG1 is a sensitive marker of the early stages of parthanatosis and a promising indicator for ELISA screening of liver carcinogenesis.