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Updated: Jul 17, 2026
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Published on: July 31, 2017
Proteomic comparison of oligodendrogliomas with and without 1pLOH
Hiroaki Okamoto1, Jie Li, Sven Gläsker
1Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, Maryland 20892-1414, USA.
Objective:
Chemoresistance is a widespread therapeutic challenge in glial tumors. The molecular basis of chemoresistance is poorly understood, precluding advances in glioma treatment and leaving gliomas among the most lethal tumors. Oligodendrogliomas provide a unique model to study the molecular basis of chemoresistance, as there are two distinct genetic subtypes with significant differences in chemosensitivity. Despite a high morphological similarity, tumors with allelic loss on the short arm of chromosome 1 (1pLOH) are more chemosensitive than those without 1pLOH.
Methods:
In order to identify candidate proteins potentially responsible for glioma chemosensitivity, we compared the proteome of four oligodendrogliomas with and five without 1pLOH using comparative proteomic profiling. Proteomic analysis was performed by two-dimensional protein gel electrophoresis and subsequent computerized gel analysis for detection of distinguishing patterns of protein expression. Differentially expressed proteins were identified using Liquid Chromatography/Mass Spectrometry. Differential expression of select proteins was confirmed by Western blotting.
Results:
We identified seven candidate proteins that are overexpressed in oligodendrogliomas without 1pLOH. Two of these proteins (glyoxalase I and Rho GDP dissociation inhibitor) have previously been shown to enhance chemoresistance in other tumors. In turn, we identified twelve overexpressed proteins in tumors with 1pLOH that have previously been reported to induce chemosensitivity in other forms of human neoplasia.
Conclusions:
These identified proteins are potential targets for pharmacological therapy and may also be useful as biomarkers for differentiation of chemoresistant and chemosensitive oligodendroglioma.
Insights
Chemoresistance in oligodendrogliomas differs between genetic subtypes. Proteomic analysis identified proteins associated with chemoresistance and chemosensitivity, offering potential therapeutic targets and biomarkers for glioma treatment.
Area of Science:
- Neuro-oncology
- Proteomics
- Molecular biology
Background:
- Chemoresistance is a major challenge in treating lethal glial tumors like gliomas.
- Oligodendrogliomas exhibit distinct genetic subtypes with varying chemosensitivity, making them a model for studying resistance.
- Tumors with 1p allelic loss (1pLOH) are more chemosensitive than those without.
Purpose of the Study:
- To identify candidate proteins responsible for chemoresistance and chemosensitivity in oligodendrogliomas.
- To compare the proteomes of oligodendrogliomas with and without 1pLOH.
Main Methods:
- Comparative proteomic profiling of oligodendrogliomas with and without 1pLOH.
- Two-dimensional protein gel electrophoresis and computerized analysis.
- Liquid Chromatography/Mass Spectrometry for protein identification.
- Western blotting for confirmation of differential protein expression.
Main Results:
- Seven proteins overexpressed in chemoresistant oligodendrogliomas (without 1pLOH) were identified, including two known to enhance chemoresistance.
- Twelve proteins overexpressed in chemosensitive oligodendrogliomas (with 1pLOH) were identified, known to induce chemosensitivity.
Conclusions:
- Identified proteins represent potential therapeutic targets for overcoming chemoresistance in gliomas.
- These proteins may serve as biomarkers to differentiate chemoresistant and chemosensitive oligodendrogliomas.
