Glioblastoma stem cells express non-canonical proteins and exclusive mesenchymal-like or non-mesenchymal-like protein signatures.

Autor: Babačić H; Department of Oncology and Pathology, Karolinska Institute, Science for Life Laboratory, Stockholm, Sweden., Galardi S; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy., Umer HM; Department of Oncology and Pathology, Karolinska Institute, Science for Life Laboratory, Stockholm, Sweden., Hellström M; Department of Immunology, Genetics and Pathology, Uppsala University, Sweden., Uhrbom L; Department of Immunology, Genetics and Pathology, Uppsala University, Sweden., Maturi N; Department of Immunology, Genetics and Pathology, Uppsala University, Sweden., Cardinali D; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy., Pellegatta S; Unit of Immunotherapy of Brain Tumors, Department of Molecular Neuro-Oncology, Foundation IRCCS, Institute for Neurology Carlo Besta, Milan, Italy., Michienzi A; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy., Trevisi G; Neurosurgical Unit, Hospital Spirito Santo, Pescara, 'G. D'Annunzio' University, Chieti, Italy., Mangiola A; Neurosurgical Unit, Hospital Spirito Santo, Pescara, 'G. D'Annunzio' University, Chieti, Italy., Lehtiö J; Department of Oncology and Pathology, Karolinska Institute, Science for Life Laboratory, Stockholm, Sweden., Ciafrè SA; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy., Pernemalm M; Department of Oncology and Pathology, Karolinska Institute, Science for Life Laboratory, Stockholm, Sweden.
Jazyk: angličtina
Zdroj: Molecular oncology [Mol Oncol] 2023 Feb; Vol. 17 (2), pp. 238-260. Date of Electronic Publication: 2023 Jan 16.
DOI: 10.1002/1878-0261.13355
Abstrakt: Glioblastoma (GBM) cancer stem cells (GSCs) contribute to GBM's origin, recurrence, and resistance to treatment. However, the understanding of how mRNA expression patterns of GBM subtypes are reflected at global proteome level in GSCs is limited. To characterize protein expression in GSCs, we performed in-depth proteogenomic analysis of patient-derived GSCs by RNA-sequencing and mass-spectrometry. We quantified > 10 000 proteins in two independent GSC panels and propose a GSC-associated proteomic signature characterizing two distinct phenotypic conditions; one defined by proteins upregulated in proneural and classical GSCs (GPC-like), and another by proteins upregulated in mesenchymal GSCs (GM-like). The GM-like protein set in GBM tissue was associated with necrosis, recurrence, and worse overall survival. Through proteogenomics, we discovered 252 non-canonical peptides in the GSCs, i.e., protein sequences that are variant or derive from genome regions previously considered non-protein-coding, including variants of the heterogeneous ribonucleoproteins implicated in RNA splicing. In summary, GSCs express two protein sets that have an inverse association with clinical outcomes in GBM. The discovery of non-canonical protein sequences questions existing gene models and pinpoints new protein targets for research in GBM.
(© 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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