Multi-Platform Classification of IDH-Wild-Type Glioblastoma Based on ERK/MAPK Pathway: Diagnostic, Prognostic and Therapeutic Implications
Glioblastoma is the most aggressive and frequent glioma in the adult population. Because current therapy regimens confer only minimal survival benefit, molecular subgrouping to stratify patient prognosis and therapy design is warranted. This study presents a multi-platform classification of glioblas...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/18/4532 |
| _version_ | 1797519953293737984 |
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| author | Maria-Magdalena Georgescu |
| author_facet | Maria-Magdalena Georgescu |
| author_sort | Maria-Magdalena Georgescu |
| collection | DOAJ |
| description | Glioblastoma is the most aggressive and frequent glioma in the adult population. Because current therapy regimens confer only minimal survival benefit, molecular subgrouping to stratify patient prognosis and therapy design is warranted. This study presents a multi-platform classification of glioblastoma by analyzing a large, ethnicity-inclusive 101-adult-patient cohort. It defines seven non-redundant IDH-wild-type glioblastoma molecular subgroups, G1–G7, corresponding to the upstream receptor tyrosine kinase (RTK) and RAS-RAF segment of the ERK/MAPK signal transduction pathway. These glioblastoma molecular subgroups are classified as G1/EGFR, G2/FGFR3, G3/NF1, G4/RAF, G5/PDGFRA, G6/Multi-RTK, and G7/Other. The comprehensive genomic analysis was refined by expression landscaping of all RTK genes, as well as of the major associated growth pathway mediators, and used to hierarchically cluster the subgroups. Parallel demographic, clinical, and histologic pattern analyses were merged with the molecular subgrouping to yield the first inclusive multi-platform classification for IDH-wild-type glioblastoma. This straightforward classification with diagnostic and prognostic significance may be readily used in neuro-oncological practice and lays the foundation for personalized targeted therapy approaches. |
| first_indexed | 2024-03-10T07:50:05Z |
| format | Article |
| id | doaj.art-2c1baed2d204445d9e0b2986030e8ef9 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T07:50:05Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2c1baed2d204445d9e0b2986030e8ef92023-11-22T12:16:39ZengMDPI AGCancers2072-66942021-09-011318453210.3390/cancers13184532Multi-Platform Classification of IDH-Wild-Type Glioblastoma Based on ERK/MAPK Pathway: Diagnostic, Prognostic and Therapeutic ImplicationsMaria-Magdalena Georgescu0NeuroMarkers PLLC, Houston, TX 77025, USAGlioblastoma is the most aggressive and frequent glioma in the adult population. Because current therapy regimens confer only minimal survival benefit, molecular subgrouping to stratify patient prognosis and therapy design is warranted. This study presents a multi-platform classification of glioblastoma by analyzing a large, ethnicity-inclusive 101-adult-patient cohort. It defines seven non-redundant IDH-wild-type glioblastoma molecular subgroups, G1–G7, corresponding to the upstream receptor tyrosine kinase (RTK) and RAS-RAF segment of the ERK/MAPK signal transduction pathway. These glioblastoma molecular subgroups are classified as G1/EGFR, G2/FGFR3, G3/NF1, G4/RAF, G5/PDGFRA, G6/Multi-RTK, and G7/Other. The comprehensive genomic analysis was refined by expression landscaping of all RTK genes, as well as of the major associated growth pathway mediators, and used to hierarchically cluster the subgroups. Parallel demographic, clinical, and histologic pattern analyses were merged with the molecular subgrouping to yield the first inclusive multi-platform classification for IDH-wild-type glioblastoma. This straightforward classification with diagnostic and prognostic significance may be readily used in neuro-oncological practice and lays the foundation for personalized targeted therapy approaches.https://www.mdpi.com/2072-6694/13/18/4532glioblastoma molecular classificationERK/MAPK pathwayPI3K/PTEN pathwayreceptor tyrosine kinaseEGFRPDGFRA |
| spellingShingle | Maria-Magdalena Georgescu Multi-Platform Classification of IDH-Wild-Type Glioblastoma Based on ERK/MAPK Pathway: Diagnostic, Prognostic and Therapeutic Implications Cancers glioblastoma molecular classification ERK/MAPK pathway PI3K/PTEN pathway receptor tyrosine kinase EGFR PDGFRA |
| title | Multi-Platform Classification of IDH-Wild-Type Glioblastoma Based on ERK/MAPK Pathway: Diagnostic, Prognostic and Therapeutic Implications |
| title_full | Multi-Platform Classification of IDH-Wild-Type Glioblastoma Based on ERK/MAPK Pathway: Diagnostic, Prognostic and Therapeutic Implications |
| title_fullStr | Multi-Platform Classification of IDH-Wild-Type Glioblastoma Based on ERK/MAPK Pathway: Diagnostic, Prognostic and Therapeutic Implications |
| title_full_unstemmed | Multi-Platform Classification of IDH-Wild-Type Glioblastoma Based on ERK/MAPK Pathway: Diagnostic, Prognostic and Therapeutic Implications |
| title_short | Multi-Platform Classification of IDH-Wild-Type Glioblastoma Based on ERK/MAPK Pathway: Diagnostic, Prognostic and Therapeutic Implications |
| title_sort | multi platform classification of idh wild type glioblastoma based on erk mapk pathway diagnostic prognostic and therapeutic implications |
| topic | glioblastoma molecular classification ERK/MAPK pathway PI3K/PTEN pathway receptor tyrosine kinase EGFR PDGFRA |
| url | https://www.mdpi.com/2072-6694/13/18/4532 |
| work_keys_str_mv | AT mariamagdalenageorgescu multiplatformclassificationofidhwildtypeglioblastomabasedonerkmapkpathwaydiagnosticprognosticandtherapeuticimplications |