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Differential expression of PDGFRB and EGFR in microvascular proliferation in glioblastoma
Guiyan Xu1, Jian Yi Li2,3
1Department of Pathology and Laboratory Medicine, North Shore University Hospital and Long Island Jewish Medical Center, Hofstra Northwell School of Medicine, Northwell Health, Lake Success, NY, USA.
Abstract:
Glioblastoma (GBM) is the highly malignant glioma and exhibits microvascular proliferation. PCR mRNA arrays and immunohistochemical stains on tissue microarray demonstrated that the expression level of PDGFRB in GBM microvascular proliferation was significantly higher than that in GBM tumor cells while the expression level of EGFR was lower in microvascular proliferation than in GBM tumor cells. PDGFRB protein was selectively expressed in pericytes in GBM microvascular proliferation. By analyzing The Cancer Genome Atlas (TCGA) datasets for GBM, it was found that genomic DNA alterations were the main reason for the high expression of EGFR in GBM tumor cells. Our miRNA microarray data showed that microRNAs (miRNAs) (miR-193b-3p, miR-518b, miR-520f-3p, and miR-506-5p) targeting PDGFRB were downregulated in microvascular proliferation, which might be the most likely reason for the high expression of PDGFRB in GBM microvascular proliferation. The increase of several miRNAs (miR-133b, miR-30b-3p, miR-145-5p, and miR-146a-5p) targeting EGFR in GBM microvascular proliferation was one of the reasons for the lack of expression of EGFR in GBM microvascular proliferation. These findings implicated that miRNAs, such as miR-506, miR-133b, miR-145, and miR-146a, that target PDGFRB or EGFR, might be potential therapeutic agents for GBM. A new generation of targeted therapeutic agents against both EGFR and PDGFRB might be developed in the future.
Insights
MicroRNAs regulate key proteins in glioblastoma (GBM) microvascular proliferation. Downregulation of miRNAs targeting PDGFRB and upregulation of miRNAs targeting EGFR contribute to GBM
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genomics
Background:
- Glioblastoma (GBM) is a highly malignant glioma characterized by microvascular proliferation.
- Understanding the molecular mechanisms driving GBM angiogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the differential expression of PDGFRB and EGFR in GBM microvascular proliferation compared to tumor cells.
- To identify the role of microRNAs (miRNAs) in regulating PDGFRB and EGFR expression in GBM.
Main Methods:
- Analysis of PCR mRNA arrays and immunohistochemical stains on tissue microarrays.
- Examination of The Cancer Genome Atlas (TCGA) datasets for GBM.
- miRNA microarray analysis to identify differentially expressed miRNAs targeting PDGFRB and EGFR.
Main Results:
- PDGFRB expression was significantly higher in GBM microvascular proliferation than in tumor cells, with selective protein expression in pericytes.
- EGFR expression was lower in GBM microvascular proliferation compared to tumor cells.
- Genomic DNA alterations correlated with high EGFR expression in GBM tumor cells.
- Downregulation of miRNAs targeting PDGFRB and upregulation of miRNAs targeting EGFR were observed in GBM microvascular proliferation.
Conclusions:
- miRNAs play a significant role in regulating PDGFRB and EGFR expression in GBM microvascular proliferation.
- Specific miRNAs targeting PDGFRB and EGFR show potential as therapeutic agents for GBM.
- Future targeted therapies could be developed to simultaneously target both EGFR and PDGFRB in GBM.
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