Investigation of metabolic features of glioblastoma tissue and the peritumoral environment using targeted metabolomics screening by LC-MS/MS and gene network analysis
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 co...
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Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders
2025-01-01
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Series: | Вавиловский журнал генетики и селекции |
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Online Access: | https://vavilov.elpub.ru/jour/article/view/4410 |
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author | N. V. Basov A. V. Adamovskaya A. D. Rogachev E. V. Gaisler P. S. Demenkov T. V. Ivanisenko A. S. Venzel S. V. Mishinov V. V. Stupak S. V. Cheresiz O. S. Oleshko E. A. Butikova A. E. Osechkova Yu. S. Sotnikova Y. V. Patrushev A. S. Pozdnyakov I. N. Lavrik V. A. Ivanisenko A. G. Pokrovsky |
author_facet | N. V. Basov A. V. Adamovskaya A. D. Rogachev E. V. Gaisler P. S. Demenkov T. V. Ivanisenko A. S. Venzel S. V. Mishinov V. V. Stupak S. V. Cheresiz O. S. Oleshko E. A. Butikova A. E. Osechkova Yu. S. Sotnikova Y. V. Patrushev A. S. Pozdnyakov I. N. Lavrik V. A. Ivanisenko A. G. Pokrovsky |
author_sort | N. V. Basov |
collection | DOAJ |
description | 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 overrepresentation 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. |
format | Article |
id | doaj-art-091cc9029b0542cb9b252c9dd2eda49c |
institution | Kabale University |
issn | 2500-3259 |
language | English |
publishDate | 2025-01-01 |
publisher | Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders |
record_format | Article |
series | Вавиловский журнал генетики и селекции |
spelling | doaj-art-091cc9029b0542cb9b252c9dd2eda49c2025-02-01T09:58:14ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592025-01-0128888289610.18699/vjgb-24-961523Investigation of metabolic features of glioblastoma tissue and the peritumoral environment using targeted metabolomics screening by LC-MS/MS and gene network analysisN. V. Basov0A. V. Adamovskaya1A. D. Rogachev2E. V. Gaisler3P. S. Demenkov4T. V. Ivanisenko5A. S. Venzel6S. V. Mishinov7V. V. Stupak8S. V. Cheresiz9O. S. Oleshko10E. A. Butikova11A. E. Osechkova12Yu. S. Sotnikova13Y. V. Patrushev14A. S. Pozdnyakov15I. N. Lavrik16V. A. Ivanisenko17A. G. Pokrovsky18N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityNovosibirsk State University; Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesN.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityNovosibirsk State UniversityNovosibirsk State University; Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesNovosibirsk State University; Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesNovosibirsk State University; Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesNovosibirsk Research Institute of Traumatology and Orthopedics named after Ya.L. Tsivyan of the Ministry of Health of the Russian FederationNovosibirsk Research Institute of Traumatology and Orthopedics named after Ya.L. Tsivyan of the Ministry of Health of the Russian FederationNovosibirsk State UniversityNovosibirsk State UniversityNovosibirsk State University; Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesN.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences; Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of SciencesN.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University; Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of SciencesNovosibirsk State University; Boreskov Institute of Catalysis of the Siberian Branch of the Russian Academy of SciencesA.E. Favorsky Irkutsk Institute of Chemistry of the Siberian Branch of the Russian Academy of SciencesInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesNovosibirsk State University; Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Kurchatov Genomic Center of ICG SB RASNovosibirsk State UniversityThe 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 overrepresentation 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.https://vavilov.elpub.ru/jour/article/view/4410glioblastomaperitumoral tissuemarkersmetabolomicslc-ms/mssphingolipidsmetabolic pathwaysgene networkscognitive system andsystem |
spellingShingle | N. V. Basov A. V. Adamovskaya A. D. Rogachev E. V. Gaisler P. S. Demenkov T. V. Ivanisenko A. S. Venzel S. V. Mishinov V. V. Stupak S. V. Cheresiz O. S. Oleshko E. A. Butikova A. E. Osechkova Yu. S. Sotnikova Y. V. Patrushev A. S. Pozdnyakov I. N. Lavrik V. A. Ivanisenko A. G. Pokrovsky 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 glioblastoma peritumoral tissue markers metabolomics lc-ms/ms sphingolipids metabolic pathways gene networks cognitive system andsystem |
title | Investigation of metabolic features of glioblastoma tissue and the peritumoral environment using targeted metabolomics screening by LC-MS/MS and gene network analysis |
title_full | Investigation of metabolic features of glioblastoma tissue and the peritumoral environment using targeted metabolomics screening by LC-MS/MS and gene network analysis |
title_fullStr | Investigation of metabolic features of glioblastoma tissue and the peritumoral environment using targeted metabolomics screening by LC-MS/MS and gene network analysis |
title_full_unstemmed | Investigation of metabolic features of glioblastoma tissue and the peritumoral environment using targeted metabolomics screening by LC-MS/MS and gene network analysis |
title_short | Investigation of metabolic features of glioblastoma tissue and the peritumoral environment using targeted metabolomics screening by LC-MS/MS and gene network analysis |
title_sort | investigation of metabolic features of glioblastoma tissue and the peritumoral environment using targeted metabolomics screening by lc ms ms and gene network analysis |
topic | glioblastoma peritumoral tissue markers metabolomics lc-ms/ms sphingolipids metabolic pathways gene networks cognitive system andsystem |
url | https://vavilov.elpub.ru/jour/article/view/4410 |
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