Advances in Molecular OncologyAdvances in Molecular OncologyУспехи молекулярной онкологии2313-805X2413-3787Publishing House ABV Press54710.17650/2313-805X-2023-10-2-117-125EXPERIMENTAL REPORTЭКСПЕРИМЕНТАЛЬНАЯ СТАТЬЯIdentification of predictive markers in the cerebrospinal fluid of patients with glioblastomaИдентификация предиктивных маркеров в спинномозговой жидкости больных глиобластомойhttps://orcid.org/0000-0002-0154-8604ArnotskayaN. E.АрноцкаяН. Е.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0001-9626-6847KushnirT. I.КушнирТ. И.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0001-7588-1066KudryavtsevI. A.КудрявцевИ. А.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-4125-7342MitrofanovA. A.МитрофановА. A.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-4160-9598BekyashevA. Kh.БекяшевА. Х.
Russian Federation

24 Kashirskoe Shosse, Moscow 115522

115522 Москва, Каширское шоссе, 24

https://orcid.org/0000-0002-0401-9900ShevchenkoV. E.ШевченкоВ. Е.
Russian Federation

Valery E. Shevchenko.

24 Kashirskoe Shosse, Moscow 115522

Шевченко Валерий Евгеньевич.

115522 Москва, Каширское шоссе, 24

vshev2015@yandex.ruN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава России150520231021171251904202310072023Copyright ©; 2023, Arnotskaya N.E., Kushnir T.I., Kudryavtsev I.A., Mitrofanov A.A., Bekyashev A.K., Shevchenko V.E.Copyright ©; 2023, Арноцкая Н.Е., Кушнир Т.И., Кудрявцев И.А., Митрофанов А.A., Бекяшев А.Х., Шевченко В.Е.2023Arnotskaya N.E., Kushnir T.I., Kudryavtsev I.A., Mitrofanov A.A., Bekyashev A.K., Shevchenko V.E.Арноцкая Н.Е., Кушнир Т.И., Кудрявцев И.А., Митрофанов А.A., Бекяшев А.Х., Шевченко В.Е.https://creativecommons.org/licenses/by/4.0https://umo.abvpress.ru/jour/article/view/547

Introduction. Glioblastoma  (GB) is not yet curable despite recent advances in the treatment of other malignant solid tumors. The management of GB is based solely on histopathological features, imaging of the tumor and its genomic analysis (somatic mutations in the isocitrate dehydrogenase genes, methylation status of the O6-methylguanine-DNA methyltransferase gene promoter). To adapt the treatment to the most recent tumor evolution, molecular information should be received regularly throughout the course of therapy. However, tumor tissue is often not available for diagnosis as the disease progresses. In this regard, the development of less invasive methods, such as analysis of the proteome of biological fluids of patients, is of particular interest. Cerebrospinal fluid (CSF) is an important source disease biomarkers to monitor the presence and progression of the disease.

Aim. To identify proteomic predictive biomarkers in the CSF of patients with GB.

Materials and methods. During the study, samples of patients’ CSF samples, high-resolution proteomic mass spectrometry, modern biochemical methods and bioinformatic technologies were used.

Results. For the first time, the analysis of proteomes of CSF samples of patients with GB obtained before and 7 days after the removal of the primary tumor was carried out. Potential biomarkers of GB have been identified. After their validation using open databases, 11 proteomic predictive markers of GB (S100A9,  S100A8, PLA2G15, PPIB, LTBP2, VIM, LAMB1, STC1, NRP1, COL6A1, HSPA5)  were selected and their role in the molecular mechanisms of gliomagenesis was assessed. Conclusion. The proposed panel of proteomic predictive CSF biomarkers in GB patients can be further used in the development of test systems for assessing the effectiveness of therapy and early detection of disease relapses.

Введение. Глиобластома (ГБ) пока неизлечима, несмотря на достижения в терапии других злокачественных солидных опухолей. Тактика лечения ГБ основывается исключительно на гистопатологических признаках, томографической визуализации опухоли и ее геномном анализе (соматические мутации в генах изоцитратдегидрогеназы, статус метилирования промотора гена O6-метилгуанин-ДНК-метилтрансфераза). для адаптации лечения к самой последней эволюции опухоли молекулярная информация должна поступать регулярно на протяжении всего курса терапии. Однако опухолевая ткань часто недоступна для диагностики при прогрессировании заболевания. в связи с этим актуальной становится разработка менее инвазивных методов, например анализа протеома биологических жидкостей пациентов. Особый интерес представляет спинномозговая жидкость (СМЖ) – важный источник биомаркеров заболевания для мониторинга наличия и прогрессирования заболевания.

Цель исследования – идентификация протеомных предиктивных биомаркеров в СМЖ больных ГБ.

Материалы и методы. В ходе исследования были использованы образцы СМЖ пациентов, протеомная масс-спектрометрия высокого разрешения, современные биохимические методы и биоинформатические технологии.

Результаты. Впервые проведен анализ протеомов образцов СМЖ больных  ГБ, полученных до и спустя 7 дней после удаления первичной опухоли. идентифицированы  потенциальные биомаркеры ГБ. после их валидации с использованием открытых баз данных отобраны 11 протеомных предиктивных маркеров ГБ (S100A9, S100A8, PLA2G15, PPIB,  LTBP2, VIM, LAMB1, STC1, NRP1, COL6A1, HSPA5)  и проведена оценка их роли в молекулярных механизмах глиомагенеза.

Заключение. Предложенная панель протеомных предиктивных биомаркеров СМЖ больных ГБ может в дальнейшем использоваться при разработке тест-систем для оценки эффективности терапии и раннего выявления рецидивов заболевания.

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