Superoxide dismutase of the peritumoral zone as a factor in the progression of various molecular profiles’ gliomas

Abstract

Background. The peritumoral zone contributes to the progression of gliomas due to its altered metabolism. Superoxide dismutase is one of the main antioxidant defense enzymes; it may be related to gliomagenesis, since the activation of free radical oxidation provokes tumor transformation of cells. Aim. Analysis of superoxide dismutase activity in different areas of the tumor depending on the status of gliomas molecular genetic markers. Material and methods. The surgical material of 20 patients with gliomas of various degrees of anaplasia was analyzed. The brain tissue of people who died as a result of trauma (6 people) served as a control. The status of tumor markers was assessed immunohistochemically. Superoxide dismutase activity and free radical activity were determined in tumor and brain tissue homogenates using Fe-induced biochemiluminescence. For statistical analysis, the computer program StatPlus 6 with the Analyst Soft Inc package was used. Data analysis was carried out using nonparametric methods of statistical processing of the material using nonparametric criteria (MannWhitney U test, KolmogorovSmirnov test, Spearman's rank correlation coefficient). Results. With active tumor growth (Grade IV), free radical activity and superoxide dismutase activity in the peritumoral zone were higher than in intact tissue. Superoxide dismutase activity in the peritumoral zone showed significant correlations: positive with the cell proliferation marker Ki-67 (rs=0.858) and negative with mutations in the isocitrate dehydrogenase (IDH) gene (rs=0.514) and methylation of the O-6-methylguanine-DNA-methyltransferase promoter (rs=0.766). The activity of the peritumoral zone enzyme differed depending on the molecular genetic profile of gliomas. Bioinformatic analysis of interactions between superoxide dismutase and molecular genetic markers of gliomas using the STRING, BioGrid, Signor, and SignaLink databases revealed the presence of mediated interactions with IDH1 with a clustering coefficient of 0.945. This level of clustering indicates the biological relationship of IDH1 with the main enzymes of the antioxidant system, superoxide dismutase and catalase. Conclusion. Significant correlations of superoxide dismutase activity in the peritumoral zone with the status of a tumor markers number and significant differences in enzyme activity in groups depending on the molecular genetic profile suggest the importance of assessing superoxide dismutase activity as a factor in the gliomas progression.