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

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

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 (Mann–Whitney U test, Kolmogorov–Smirnov 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.

Full Text

Restricted Access

About the authors

Elena I. Murach

Privolzhsky Research Medical University

Email: elena_murach@mail.ru
ORCID iD: 0000-0002-8472-5820
SPIN-code: 3961-6077

Cand. Sci. (Biol.), Assistant, Depart. of Biochemistry named after G.Ya. Gorodisskaya

Russian Federation, Nizhny Novgorod, Russia

Igor A. Medyanik

Privolzhsky Research Medical University

Email: med_neuro@inbox.ru
ORCID iD: 0000-0002-7519-0959

M.D., D. Sci. (Med.), Senior Researcher, Group of Microneurosurgery, University Clinic; Assoc. Prof., Depart. of Traumatology, Orthopedics and Neurosurgery named after M.V. Kolokoltsev

Russian Federation, Nizhny Novgorod, Russia

Artem S. Grishin

Privolzhsky Research Medical University

Email: zhest8242@mail.ru
ORCID iD: 0000-0001-7885-8662

M.D., pathologist

Russian Federation, Nizhny Novgorod, Russia

Mikhail M. Kontorshchikov

Privolzhsky Research Medical University

Author for correspondence.
Email: kontormm9@gmail.com
ORCID iD: 0000-0002-0262-5448

student

Russian Federation, Nizhny Novgorod, Russia

Dariya M. Badanina

National Research Nizhny Novgorod State University named after N.I. Lobachevsky

Email: dariyambadanina@mail.ru
ORCID iD: 0000-0002-3761-3746

MS Student

Russian Federation, Nizhny Novgorod, Russia

References

  1. Louis DN, Perry A, Wesseling P, Brat DJ, Cree IA, Figarella-Branger D, Hawkins C, Ng HK, Pfister SM, Reifenberger G, Soffietti R, von Deimling A, Ellison DW. The 2021 WHO classification of tumors of the central nervous system: A summary. Neuro Oncol. 2021;23(8):1231–1251. doi: 10.1093/neuonc/noab106.
  2. Friedman J. Why is the nervous system vulnerable to oxidative stress? In: Oxidative stress and free radical damage in neurology. Totowa, New Jersey: Humana Press; 2010. р. 19–27. doi: 10.1007/978-1-60327-514-9_2.
  3. Fridovich I. Superoxide dismutase. In: Encyclopedia of Biological Chemistry. New York City: Academic Press; 2013. р. 352–354.
  4. Altieri R, Barbagallo D, Certo F, Broggi G, Ragusa M, Di Pietro C, Caltabiano R, Magro G, Peschillo S, Purrello M, Barbagallo G. Peritumoral microenvironment in high-grade gliomas: From FLAIRectomy to microglia-glioma cross-talk. Brain Sci. 2021;11(20):200. doi: 10.3390/brainsci11020200.
  5. Dizhe GP, Eshchenko ND, Dizhe AA, Krasovskaya IE. Vvedenie v tekhniku biokhimicheskogo eksperimenta. (Introduction to the technique of biochemical experiment.) SPb.: St. Petersburg University; 2003. 56 p. (In Russ.)
  6. Kuz'mina EI, Nelyubin AS, Hennikova MK. Application of induced chemiluminescence to eva-luate free radical reactions in biological substrates. In: Mezhvuzovskiy sbornik biokhimii i biofiziki mikroorganizmov. (Interuniversity collection on biochemistry and biophysics of microorganisms.) Gorkiy: GMI; 1983. p. 179–183. (In Russ.)
  7. Nishikimi M, Appa N, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenacinemethosulfate and molecular. Biochem Biophys Res Commun. 1972;4(3):849–854. doi: 10.1016/s0006-291x(72)80218-3.
  8. Yoda RA, Marxen T, Longo L, Ene C, Wirsching HG, Keene D, Holland EC, Cimino PJ. Mitotic index thresholds do not predict clinical outcome for IDH-mutant astrocytoma. J Neuropathol Exp Neurol. 2019;78(11):1002–1010. doi: 10.1093/jnen/nlz082.
  9. Kim YS, Vallur PG, Phaëton R, Mythreye K, Hempel N. Insights into the dichotomous regulation of SOD2 in cancer. Antioxidants (Basel). 2017;6(4):86. doi: 10.3390/antiox6040086.
  10. Aoki K, Natsume A. Overview of DNA methylation in adult diffuse gliomas. Brain Tumor Pathol. 2019;36(2):84–91. doi: 10.1007/s10014-019-00339-w.
  11. Malta TM, Souza de CF, Sabedot TS, Silva TC, Mosella MS, Kalkanis SN, Snyder J, Castro A-VB, Noushmehr H. Glioma CpG island methylator phenotype (G-CIMP): Biological and clinical implications. Neuro Oncol. 2018;20(5):608–620. doi: 10.1093/neuonc/nox183.
  12. Aubrey BJ, Strasser A, Kelly GL. Tumor-suppressor functions of the TP53 pathway. Cold Spring Harb Perspect Med. 2016;6(5):a026062. doi: 10.1101/cshperspect.a026062.
  13. Al-Khallaf H. Isocitrate dehydrogenases in physiology and cancer: Biochemical and molecular insight. Cell Biosci. 2017;7:37. doi: 10.1186/s13578-017-0165-3.
  14. Clark O, Yen K, Mellinghoff IK. Molecular pathways: Isocitrate dehydrogenase mutations in cancer. Clin Cancer Res. 2016;22(8):1837–1842. doi: 10.1158/1078-0432.CCR-13-1333.
  15. Johannessen TA, Mukherjee J, Viswanath P, Ohba S, Ronen SM, Bjerkvig R, Pieper RO. Rapid conversion of mutant IDH1 from driver to passenger in a model of human gliomagenesis. Mol Cancer Res. 2016;14(10):976–983. doi: 10.1158/1541-7786.MCR-16-0141.

Supplementary files

Supplementary Files
Action
1. JATS XML
2. Рис. 1. Медианы и межквартильные расстояния активности супероксиддисмутазы (СОД) в ткани глиом в зависимости от величины митотического индекса Ki-67. Есть значимые различия по активности СОД между группами с низким и высоким митотическим индексом Ki-67 в непоражённой ткани головного мозга вокруг опухоли (U-критерий Манна–Уитни р=0,002; критерий Колмогорова–Смирнова р=0,005) и перитуморальной зоне опухоли (U-критерий Манна–Уитни р=0,001; критерий Колмогорова–Смирнова р=0,005). *Различия статистически значимы

Download (29KB)
3. Рис. 2. Медианы и межквартильные расстояния активности супероксиддисмутазы (СОД) в ткани глиом в зависимости от промотора гена О-6-метилгуанин-ДНК-метилтрансферазы MGMT, который осуществляет репарацию дезоксирибонуклеиновой кислоты (ДНК). Есть значимые различия по активности СОД между группами с метилированием MGMT в непоражённой ткани головного мозга вокруг опухоли (U-критерий Манна–Уитни р=0,04; критерий Колмогорова–Смирнова р=0,03) и перитуморальной зоне опухоли (U-критерий Манна–Уитни р=0,008; критерий Колмогорова–Смирнова р=0,009). *Различия статистически значимы

Download (31KB)

© 2023 Eco-Vector





This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies