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Tumour Biol. 2016 Aug;37(8):10577-86. doi: 10.1007/s13277-016-4968-3. Epub 2016 Feb 9.

Differential expression of PDGFRB and EGFR in microvascular proliferation in glioblastoma.

Xu G1, Li JY2,3.

Author information

1
Department 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.
2
Department 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. jli2@nshs.edu.
3
Cancer Institute, Northwell Health, Lake Success, NY, USA. jli2@nshs.edu.

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.

KEYWORDS:

EGFR; Glioblastoma; MicroRNA (miRNA); Microvascular proliferation; PCR array; PDGFRB; Tissue microarray

PMID:
26857280
DOI:
10.1007/s13277-016-4968-3
[Indexed for MEDLINE]

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