: 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.

Glioblastoma stem cells express non-canonical proteins and exclusive mesenchymal-like or non-mesenchymal-like protein signatures / Babačić, Haris; Galardi, Silvia; Umer, Husen M; Hellström, Mats; Uhrbom, Lene; Maturi, Nagaprathyusha; Cardinali, Deborah; Pellegatta, Serena; Michienzi, Alessandro; Trevisi, Gianluca; Mangiola, Annunziato; Lehtiö, Janne; Ciafrè, Silvia Anna; Pernemalm, Maria. - In: MOLECULAR ONCOLOGY. - ISSN 1878-0261. - 17:2(2023), pp. 238-260. [10.1002/1878-0261.13355]

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

Cardinali, Deborah;
2023

Abstract

: 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.
2023
glioblastoma stem cells; mesenchymal; proneural; proteogenomics; proteomics; signature
01 Pubblicazione su rivista::01a Articolo in rivista
Glioblastoma stem cells express non-canonical proteins and exclusive mesenchymal-like or non-mesenchymal-like protein signatures / Babačić, Haris; Galardi, Silvia; Umer, Husen M; Hellström, Mats; Uhrbom, Lene; Maturi, Nagaprathyusha; Cardinali, Deborah; Pellegatta, Serena; Michienzi, Alessandro; Trevisi, Gianluca; Mangiola, Annunziato; Lehtiö, Janne; Ciafrè, Silvia Anna; Pernemalm, Maria. - In: MOLECULAR ONCOLOGY. - ISSN 1878-0261. - 17:2(2023), pp. 238-260. [10.1002/1878-0261.13355]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1670678
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 3
social impact