Investigation of Metabolic Features of Glioblastoma Tissue and the Peritumoral Environment Using Targeted Metabolomics Screening by LC-MS/MS and Gene Network Analysis | Sciact - CRIS-system of Boreskov Institute of Catalysis

Investigation of Metabolic Features of Glioblastoma Tissue and the Peritumoral Environment Using Targeted Metabolomics Screening by LC-MS/MS and Gene Network Analysis Full article

Journal

Вавиловский журнал генетики и селекции
ISSN: 2500-0462 , E-ISSN: 2500-3259

Output data

Year: 2025, Volume: 28, Number: 8, Pages: 882-896 Pages count : 15 DOI: 10.18699/vjgb-24-96

Tags

glioblastoma; peritumoral tissue; markers; metabolomics; LC-MS/MS; sphingolipids; metabolic pathways; gene networks; cognitive system ANDSystem.

Authors

Basov N.V. ^1,2 , Adamovskaya A.V. ^2,3 , Rogachev A.D. ^1,2 , Gaisler E.V. ² , Demenkov P.S. ^2,3 , Ivanisenko T.V. ^2,3 , Venzel A.S. ^2,3 , Mishinov S.V. ⁴ , Stupak V.V. ⁴ , Cheresiz S.V. ² , Oleshko O.S. ² , Butikova E.A. ^2,5 , Osechkova A.E. ^1,6 , Sotnikova Yu.S. ^1,2,6 , Patrushev Y.V. ^2,6 , Pozdnyakov A.S. ⁷ , Lavrik I.N. ³ , Ivanisenko V.A. ^2,3,8 , Pokrovsky A.G. ²

Affiliations

1	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
2	Novosibirsk State University, Novosibirsk, Russia
3	Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
4	Novosibirsk Research Institute of Traumatology and Orthopedics named after Ya.L. Tsivyan of the Ministry of Health of the Russian Federation, Novosibirsk, Russia
5	Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
6	Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
7	A.E. Favorsky Irkutsk Institute of Chemistry of the Siberian Branch of the Russian Academy of Sciences, Irkutsk, Russia
8	Kurchatov Genomic Center of ICG SB RAS, Novosibirsk, Russia

Funding (3)

1	Ministry of Science and Higher Education of the Russian Federation	FWUR-2024-0032
2	Ministry of Science and Higher Education of the Russian Federation	FSUS-2020-0035
3	Ministry of Science and Higher Education of the Russian Federation	FWNR-2022-0020 (122042000126-6)

The metabolomic profiles of glioblastoma and surrounding brain tissue, comprising 17 glioblastoma samples and 15 peritumoral tissue samples, were thoroughly analyzed in this investigation. The LC-MS/MS method was used to analyze over 400 metabolites, revealing significant variations in metabolite content between tumor and peritumoral tissues. Statistical analyses, including the Mann–Whitney and Cucconi tests, identified several metabolites, particularly ceramides, that showed significant differences between glioblastoma and peritumoral tissues. Pathway analysis using the KEGG database, conducted with MetaboAnalyst 6.0, revealed a statistically significant overrepresentation of sphingolipid metabolism, suggesting a critical role of these lipid molecules in glioblastoma pathogenesis. Using computational systems biology and artificial intelligence methods implemented in a cognitive platform, ANDSystem, molecular genetic regulatory pathways were reconstructed to describe potential mechanisms underlying the dysfunction of sphingolipid metabolism enzymes. These reconstructed pathways were integrated into a regulatory gene network comprising 15 genes, 329 proteins, and 389 interactions. Notably, 119 out of the 294 proteins regulating the key enzymes of sphingolipid metabolism were associated with glioblastoma. Analysis of the over representation of Gene Ontology biological processes revealed the statistical significance of 184 processes, including apoptosis, the NF-kB signaling pathway, proliferation, migration, angiogenesis, and pyroptosis, many of which play an important role in oncogenesis. The findings of this study emphasize the pivotal role of sphingolipid metabolism in glioblastoma development and open new prospects for therapeutic approaches modulating this metabolism.

Basov N.V. , Adamovskaya A.V. , Rogachev A.D. , Gaisler E.V. , Demenkov P.S. , Ivanisenko T.V. , Venzel A.S. , Mishinov S.V. , Stupak V.V. , Cheresiz S.V. , Oleshko O.S. , Butikova E.A. , Osechkova A.E. , Sotnikova Y.S. , Patrushev Y.V. , Pozdnyakov A.S. , Lavrik I.N. , Ivanisenko V.A. , Pokrovsky A.G.
Investigation of Metabolic Features of Glioblastoma Tissue and the Peritumoral Environment Using Targeted Metabolomics Screening by LC-MS/MS and Gene Network Analysis
Вавиловский журнал генетики и селекции. 2025. V.28. N8. P.882-896. DOI: 10.18699/vjgb-24-96 WOS Scopus РИНЦ OpenAlex

Web of science:	WOS:001444081000008
Scopus:	2-s2.0-85217256182
Elibrary:	80256559
OpenAlex:	W4407057429

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