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Characterizing the Linkage of Systemic Hypoxia and Angiogenesis in High-Grade Glioma to Define the Changes in Tumor Microenvironment for Predicting Prognosis.
- Source :
-
Journal of molecular neuroscience : MN [J Mol Neurosci] 2024 Jul 05; Vol. 74 (3), pp. 63. Date of Electronic Publication: 2024 Jul 05. - Publication Year :
- 2024
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Abstract
- High-grade gliomas (HGG) comprising WHO grades 3 and 4 have a poor overall survival (OS) that has not improved in the past decade. Herein, markers representing four components of the tumor microenvironment (TME) were identified to define their linked expression in TME and predict the prognosis in HGG, namely, interleukin6 (IL6, inflammation), inducible nitric oxide synthase(iNOS), heat shock protein-70 (HSP70, hypoxia), vascular endothelial growth receptor (VEGF), and endothelin1 (ET1) (angiogenesis) and matrix metalloprotease-14 (MMP14) and intercellular adhesion molecule1 (ICAM1, extracellular matrix). To establish a non-invasive panel of biomarkers for precise prognostication in HGG. Eighty-six therapy-naive HGG patients with 45 controls were analyzed for the defined panel. Systemic expression of extracellular/secretory biomarkers was screened dot-immune assay (DIA), quantified by ELISA, and validated by immunocytochemistry (ICC). Expression of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 was found to be positively associated with grade. Quantification of circulating levels of the markers by ELISA and ICC presented a similar result. The biomarkers were observed to negatively correlate with OS (pā<ā0.0001). Cox-regression analysis yielded all biomarkers as good prognostic indicators and independent of confounders. On applying combination statistics, the biomarker panel achieved higher sensitivity than single markers to define survival. The intra-association of all seven biomarkers was significant, hinting of a cross-talk between the TME components and a hypoxia driven systemic inflammation upregulating the expression of other components. This is a first ever experimental study of a marker panel that can distinguish between histopathological grades and also delineate differential survival using liquid biopsy, suggesting that markers of hypoxia can be a cornerstone for personalized therapy. The panel of biomarkers of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 holds promise for prognostication in HGG.<br /> (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Humans
Female
Male
Middle Aged
Adult
Intercellular Adhesion Molecule-1 metabolism
Intercellular Adhesion Molecule-1 blood
Interleukin-6 metabolism
Interleukin-6 blood
Matrix Metalloproteinase 14 metabolism
Vascular Endothelial Growth Factor A metabolism
Vascular Endothelial Growth Factor A blood
Endothelin-1 metabolism
Endothelin-1 blood
Aged
Tumor Hypoxia
Prognosis
Angiogenesis
Tumor Microenvironment
Glioma metabolism
Glioma pathology
Brain Neoplasms metabolism
Brain Neoplasms pathology
HSP70 Heat-Shock Proteins metabolism
HSP70 Heat-Shock Proteins blood
Biomarkers, Tumor metabolism
Nitric Oxide Synthase Type II metabolism
Neovascularization, Pathologic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1559-1166
- Volume :
- 74
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of molecular neuroscience : MN
- Publication Type :
- Academic Journal
- Accession number :
- 38967861
- Full Text :
- https://doi.org/10.1007/s12031-024-02240-4