Platelet-derived growth factor receptor α/glial fibrillary acidic protein expressing peritumoral astrocytes associate with shorter median overall survival in glioblastoma patients.
Adolescent
Adult
Aged
Aged, 80 and over
Astrocytes
/ metabolism
Biomarkers, Tumor
/ metabolism
Brain Neoplasms
/ genetics
Child
Female
Glial Fibrillary Acidic Protein
/ genetics
Glioblastoma
/ genetics
Humans
In Situ Hybridization, Fluorescence
Male
Middle Aged
Prognosis
Receptors, Platelet-Derived Growth Factor
/ genetics
Survival Rate
Tumor Microenvironment
/ physiology
Young Adult
PDGFRα
astrocyte
biomarker
cell subset
glioblastoma
tumor microenvironment
Journal
Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
21
05
2019
revised:
07
11
2019
accepted:
11
11
2019
pubmed:
27
11
2019
medline:
11
6
2021
entrez:
27
11
2019
Statut:
ppublish
Résumé
The microenvironment and architecture of peritumoral tissue have been suggested to affect permissiveness for infiltration of malignant cells. Astrocytes constitute a heterogeneous population of cells and have been linked to proliferation, migration, and drug sensitivity of glioblastoma (GBM) cells. Through double-immunohistochemical staining for platelet-derived growth factor receptor α (PDGFRα) and glial fibrillary acidic protein (GFAP), this study explored the intercase variability among 45 human GBM samples regarding density of GFAP+ peritumoral astrocytes and a subset of GFAP+ peritumoral astrocyte-like cells also expressing PDGFRα. Large intercase variability regarding the total peritumoral astrocyte density and the density of PDGFRα+/GFAP+ peritumoral astrocyte-like cells was detected. DNA fluorescence in situ hybridization analyses for commonly altered genetic tumor markers supported the interpretation that these cells represented a genetically unaffected host cell subset referred to as PDGFRα+/GFAP+ peritumoral astrocytes. The presence of PDGFRα+/GFAP+ peritumoral astrocytes was significantly positively correlated to older patient age and peritumoral astrocyte density, but not to other established prognostic factors. Notably, presence of PDGFRα+/GFAP+ peritumoral astrocytes, but not peritumoral astrocyte density, was associated with significantly shorter patient overall survival. The prognostic association of PDGFRα+/GFAP+ peritumoral astrocytes was confirmed in multivariable analyses. This exploratory study thus demonstrates previously unrecognized intercase variability and prognostic significance of peritumoral abundance of a novel PDGFRα+ subset of GFAP+ astrocytes. Findings suggest clinically relevant roles of the microenvironment of peritumoral GBM tissue and encourage further characterization of the novel astrocyte subset with regard to origin, function, and potential as biomarker and drug target.
Substances chimiques
Biomarkers, Tumor
0
Glial Fibrillary Acidic Protein
0
Receptors, Platelet-Derived Growth Factor
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
979-988Informations de copyright
© 2019 Wiley Periodicals, Inc.
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