Изучение особенностей метаболизма тканей глиобластомы и перитуморального пространства при использовании таргетированного метаболомного скрининга методом ВЭЖХ-МС/МС и генных сетей

В ходе исследования проведен комплексный анализ метаболомных профилей глиобластомы и прилегающей ткани головного мозга, включавший 17 образцов глиобластомы и 15 образцов перитумо­ральной ткани. С использованием метода ВЭЖХ-МС/МС было проанализировано более 400 метаболитов, что позволило выявить значимые различия в их содержании между опухолевой и перитуморальной тканями. Статистический анализ, включавший тесты Манна–Уитни и Куккони, показал, что существенное количество метаболитов, в частности церамиды, значимо различается в тканях глиобластомы и перитуморального про­странства. Анализ метаболических путей из базы данных KEGG, выполненный с помощью MetaboAnalyst 6.0, выявил статистически значимую перепредставленность метаболизма сфинголипидов, что указывает на важ­ную роль этих липидных молекул в патогенезе глиобластомы. С использованием методов компьютерной системной биологии и искусственного интеллекта, реализованных в когнитивной системе ANDSystem, ре­конструированы молекулярно-генетические регуляторные пути, описывающие потенциальные механизмы нарушения функции ферментов метаболизма сфинголипидов. Реконструированные пути были объединены в регуляторную генную сеть. Данная сеть включала 15 генов, 329 белков и 389 взаимодействий, при этом 119 из 294 белков, регулирующих ключевые ферменты сфинголипидного метаболизма, оказались ассоции­рованы с глиобластомой. Анализ перепредставленности биологических процессов Gene Ontology показал статистическую значимость 184 процессов, в том числе апоптоза, сигнального пути NF-κB, пролиферации, миграции, ангиогенеза и пироптоза, многие из которых играют важную роль в онкогенезе. Результаты иссле­дования подчеркивают ключевую роль метаболизма сфинголипидов в развитии глиобластомы и открывают новые перспективы для разработки терапевтических подходов, направленных на его модуляцию.

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