PMID- 24330824 OWN - NLM STAT- MEDLINE DCOM- 20140625 LR - 20211021 IS - 1755-8794 (Electronic) IS - 1755-8794 (Linking) VI - 6 DP - 2013 Dec 15 TI - Correlation of WWOX, RUNX2 and VEGFA protein expression in human osteosarcoma. PG - 56 LID - 10.1186/1755-8794-6-56 [doi] 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. FAU - Yang, Jilong AU - Yang J AD - Department of Bone and Soft Tissue Tumor, Tianjin Medical University Cancer Hospital & Institute, Tianjin 300060, China. yangjilong@tjmuch.com. FAU - Zhao, Linru AU - Zhao L FAU - Tian, Wei AU - Tian W FAU - Liao, Zhichao AU - Liao Z FAU - Zheng, Hong AU - Zheng H FAU - Wang, Guowen AU - Wang G FAU - Chen, Kexin AU - Chen K LA - eng GR - CA016672/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20131215 PL - England TA - BMC Med Genomics JT - BMC medical genomics JID - 101319628 RN - 0 (Core Binding Factor Alpha 1 Subunit) RN - 0 (Tumor Suppressor Proteins) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - EC 1.- (Oxidoreductases) RN - EC 1.1.1.- (WW Domain-Containing Oxidoreductase) RN - EC 1.1.1.- (WWOX protein, human) SB - IM MH - Adolescent MH - Adult MH - Bone Neoplasms/*genetics/metabolism/pathology MH - Core Binding Factor Alpha 1 Subunit/genetics/*metabolism MH - Female MH - Gene Dosage MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Male MH - Osteosarcoma/*genetics/metabolism/pathology MH - Oxidoreductases/genetics/*metabolism MH - Tumor Suppressor Proteins/genetics/*metabolism MH - Vascular Endothelial Growth Factor A/genetics/*metabolism MH - WW Domain-Containing Oxidoreductase MH - Young Adult PMC - PMC3878685 EDAT- 2013/12/18 06:00 MHDA- 2014/06/26 06:00 PMCR- 2013/12/15 CRDT- 2013/12/17 06:00 PHST- 2013/01/05 00:00 [received] PHST- 2013/12/10 00:00 [accepted] PHST- 2013/12/17 06:00 [entrez] PHST- 2013/12/18 06:00 [pubmed] PHST- 2014/06/26 06:00 [medline] PHST- 2013/12/15 00:00 [pmc-release] AID - 1755-8794-6-56 [pii] AID - 10.1186/1755-8794-6-56 [doi] PST - epublish SO - BMC Med Genomics. 2013 Dec 15;6:56. doi: 10.1186/1755-8794-6-56.