Correlation of WWOX, RUNX2 and VEGFA protein expression in human osteosarcoma

Jilong Yang, Linru Zhao, Wei Tian, Zhichao Liao, Hong Zheng, Guowen Wang, Kexin Chen

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: To investigate associations between WW domain-containing oxidoreductase (WWOX), runt-related transcription factor 2 (RUNX2) and vascular endothelial growth factor alpha (VEGFA) in human osteosarcoma (OS). Methods. Copy number aberrations of WWOX, RUNX2and VEGFA genes were detected by microarray comparative genomic hybridization (aCGH) in 10 fresh OS tissue samples. VEGFA gene alterations were also investigated and validated by fluorescence in situ hybridization (FISH) in 54 formalin-fixed and paraffin-embedded (FFPE) OS samples. Protein expression of WWOX, RUNX2 and VEGFA were examined in 54 FFPE OS samples by immunohistochemistry (IHC). Results: Analysis of previously published OS aCGH data (GSE9654) and aCGH data from this study (GSE19180) identified significant deletion of WWOX in 30% (6/20) of OS samples, whilst significant increase in both RUNX2 and VEGFA gene copy numbers were detected in 55% (11/20) and 60% (12/20) of OS samples, respectively. FISH demonstrated increased VEGFA gene copy number in 65.9% (31/47) of evaluable samples, in either focal or large fragment forms. Compared with positive expression of WWOX in 38.9% of the OS samples, positive expression of RUNX2 and VEGFA protein was found in 48.1 and 75.9% of samples. Although there was no significant association between gene copy number aberration and protein expression for WWOX and RUNX2, significant positive correlation between increased VEGFA gene copy number and VEGFA protein expression was observed. Although there was no significant reverse association between WWOX and RUNX2 expression, a significantly positive relationship was observed between RUNX2 and VEGFA protein expression. Conclusions: Our data show increased RUNX2 and VEGFA gene copy numbers and elevation of their respective proteins in human OS. Positive correlation of RUNX2 and VEGFA suggests that both increased VEGFA gene copy number and RUNX2 overexpression facilitate increased expression of VEGFA.

Original languageEnglish (US)
Article number56
JournalBMC medical genomics
Volume6
Issue number1
DOIs
StatePublished - Dec 15 2013

Fingerprint

Osteosarcoma
Vascular Endothelial Growth Factor A
Gene Dosage
Proteins
Fluorescence In Situ Hybridization
Paraffin
Formaldehyde
Comparative Genomic Hybridization
Genes
Oxidoreductases
Transcription Factors
Immunohistochemistry

Keywords

  • Gene amplification
  • Osteosarcoma
  • RUNX2
  • VEGFA
  • WWOX
  • aCGH,FISH

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Correlation of WWOX, RUNX2 and VEGFA protein expression in human osteosarcoma. / Yang, Jilong; Zhao, Linru; Tian, Wei; Liao, Zhichao; Zheng, Hong; Wang, Guowen; Chen, Kexin.

In: BMC medical genomics, Vol. 6, No. 1, 56, 15.12.2013.

Research output: Contribution to journalArticle

Yang, Jilong ; Zhao, Linru ; Tian, Wei ; Liao, Zhichao ; Zheng, Hong ; Wang, Guowen ; Chen, Kexin. / Correlation of WWOX, RUNX2 and VEGFA protein expression in human osteosarcoma. In: BMC medical genomics. 2013 ; Vol. 6, No. 1.
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abstract = "Background: To investigate associations between WW domain-containing oxidoreductase (WWOX), runt-related transcription factor 2 (RUNX2) and vascular endothelial growth factor alpha (VEGFA) in human osteosarcoma (OS). Methods. Copy number aberrations of WWOX, RUNX2and VEGFA genes were detected by microarray comparative genomic hybridization (aCGH) in 10 fresh OS tissue samples. VEGFA gene alterations were also investigated and validated by fluorescence in situ hybridization (FISH) in 54 formalin-fixed and paraffin-embedded (FFPE) OS samples. Protein expression of WWOX, RUNX2 and VEGFA were examined in 54 FFPE OS samples by immunohistochemistry (IHC). Results: Analysis of previously published OS aCGH data (GSE9654) and aCGH data from this study (GSE19180) identified significant deletion of WWOX in 30{\%} (6/20) of OS samples, whilst significant increase in both RUNX2 and VEGFA gene copy numbers were detected in 55{\%} (11/20) and 60{\%} (12/20) of OS samples, respectively. FISH demonstrated increased VEGFA gene copy number in 65.9{\%} (31/47) of evaluable samples, in either focal or large fragment forms. Compared with positive expression of WWOX in 38.9{\%} of the OS samples, positive expression of RUNX2 and VEGFA protein was found in 48.1 and 75.9{\%} of samples. Although there was no significant association between gene copy number aberration and protein expression for WWOX and RUNX2, significant positive correlation between increased VEGFA gene copy number and VEGFA protein expression was observed. Although there was no significant reverse association between WWOX and RUNX2 expression, a significantly positive relationship was observed between RUNX2 and VEGFA protein expression. Conclusions: Our data show increased RUNX2 and VEGFA gene copy numbers and elevation of their respective proteins in human OS. Positive correlation of RUNX2 and VEGFA suggests that both increased VEGFA gene copy number and RUNX2 overexpression facilitate increased expression of VEGFA.",
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T1 - Correlation of WWOX, RUNX2 and VEGFA protein expression in human osteosarcoma

AU - Yang, Jilong

AU - Zhao, Linru

AU - Tian, Wei

AU - Liao, Zhichao

AU - Zheng, Hong

AU - Wang, Guowen

AU - Chen, Kexin

PY - 2013/12/15

Y1 - 2013/12/15

N2 - Background: To investigate associations between WW domain-containing oxidoreductase (WWOX), runt-related transcription factor 2 (RUNX2) and vascular endothelial growth factor alpha (VEGFA) in human osteosarcoma (OS). Methods. Copy number aberrations of WWOX, RUNX2and VEGFA genes were detected by microarray comparative genomic hybridization (aCGH) in 10 fresh OS tissue samples. VEGFA gene alterations were also investigated and validated by fluorescence in situ hybridization (FISH) in 54 formalin-fixed and paraffin-embedded (FFPE) OS samples. Protein expression of WWOX, RUNX2 and VEGFA were examined in 54 FFPE OS samples by immunohistochemistry (IHC). Results: Analysis of previously published OS aCGH data (GSE9654) and aCGH data from this study (GSE19180) identified significant deletion of WWOX in 30% (6/20) of OS samples, whilst significant increase in both RUNX2 and VEGFA gene copy numbers were detected in 55% (11/20) and 60% (12/20) of OS samples, respectively. FISH demonstrated increased VEGFA gene copy number in 65.9% (31/47) of evaluable samples, in either focal or large fragment forms. Compared with positive expression of WWOX in 38.9% of the OS samples, positive expression of RUNX2 and VEGFA protein was found in 48.1 and 75.9% of samples. Although there was no significant association between gene copy number aberration and protein expression for WWOX and RUNX2, significant positive correlation between increased VEGFA gene copy number and VEGFA protein expression was observed. Although there was no significant reverse association between WWOX and RUNX2 expression, a significantly positive relationship was observed between RUNX2 and VEGFA protein expression. Conclusions: Our data show increased RUNX2 and VEGFA gene copy numbers and elevation of their respective proteins in human OS. Positive correlation of RUNX2 and VEGFA suggests that both increased VEGFA gene copy number and RUNX2 overexpression facilitate increased expression of VEGFA.

AB - Background: To investigate associations between WW domain-containing oxidoreductase (WWOX), runt-related transcription factor 2 (RUNX2) and vascular endothelial growth factor alpha (VEGFA) in human osteosarcoma (OS). Methods. Copy number aberrations of WWOX, RUNX2and VEGFA genes were detected by microarray comparative genomic hybridization (aCGH) in 10 fresh OS tissue samples. VEGFA gene alterations were also investigated and validated by fluorescence in situ hybridization (FISH) in 54 formalin-fixed and paraffin-embedded (FFPE) OS samples. Protein expression of WWOX, RUNX2 and VEGFA were examined in 54 FFPE OS samples by immunohistochemistry (IHC). Results: Analysis of previously published OS aCGH data (GSE9654) and aCGH data from this study (GSE19180) identified significant deletion of WWOX in 30% (6/20) of OS samples, whilst significant increase in both RUNX2 and VEGFA gene copy numbers were detected in 55% (11/20) and 60% (12/20) of OS samples, respectively. FISH demonstrated increased VEGFA gene copy number in 65.9% (31/47) of evaluable samples, in either focal or large fragment forms. Compared with positive expression of WWOX in 38.9% of the OS samples, positive expression of RUNX2 and VEGFA protein was found in 48.1 and 75.9% of samples. Although there was no significant association between gene copy number aberration and protein expression for WWOX and RUNX2, significant positive correlation between increased VEGFA gene copy number and VEGFA protein expression was observed. Although there was no significant reverse association between WWOX and RUNX2 expression, a significantly positive relationship was observed between RUNX2 and VEGFA protein expression. Conclusions: Our data show increased RUNX2 and VEGFA gene copy numbers and elevation of their respective proteins in human OS. Positive correlation of RUNX2 and VEGFA suggests that both increased VEGFA gene copy number and RUNX2 overexpression facilitate increased expression of VEGFA.

KW - Gene amplification

KW - Osteosarcoma

KW - RUNX2

KW - VEGFA

KW - WWOX

KW - aCGH,FISH

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