Angiogenic profile of soft tissue sarcomas based on analysis of circulating factors and microarray gene expression Journal Article
| Authors: | Yoon, S. S.; Segal, N. H.; Park, P. J.; Detwiller, K. Y.; Fernando, N. T.; Ryeom, S. W.; Brennan, M. F.; Singer, S. |
| Article Title: | Angiogenic profile of soft tissue sarcomas based on analysis of circulating factors and microarray gene expression |
| Abstract: | Background: Broader understanding of diverse angiogenic pathways in a particular cancer can lead to better utilization of anti-angiogenic therapies. The aim of this study was to develop profiles of angiogenesis-related gene and protein expression for various histologic subtypes of soft tissue sarcomas (STS) growing in different sites. Materials and methods: Plasma levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiopoietin 2 (Ang2), and leptin were determined in 108 patients with primary STS. Gene expression patterns were analyzed in 38 STS samples and 13 normal tissues using oligonucleotide microarrays. Results: VEGF and bFGF plasma levels were elevated 10-13 fold in STS patients compared to controls. VEGF levels were broadly elevated while bFGF levels were higher in patients with fibrosarcomas and leiomyosarcomas. Ang2 levels correlated with tumor size and were most elevated for tumors located in the trunk, while leptin levels were highest in patients with liposarcomas. Hierarchical clustering of microarray data based on angiogenesis-related gene expression demonstrated that histologic subtypes of STS often shared similar expression patterns, and these patterns were distinctly different from those of normal tissues. Matrix metalloproteinase 2, platelet-derived growth factor receptor, α and Notch 4 were among several genes that were up-regulated at least 7-fold in STS. Conclusions: STS demonstrate significant heterogeneity in their angiogenic profiles based on size, histologic subtype, and location of tumor growth, which may have implications for anti-angiogenic strategies. Comparison of STS to normal tissues reveals a panel of upregulated genes that may be targets for future therapies. © 2006 Elsevier Inc. All rights reserved. |
| Keywords: | vasculotropin; adult; clinical article; controlled study; human tissue; vascular endothelial growth factor a; cancer patient; leptin; tumor localization; cluster analysis; gene expression; tumor volume; platelet derived growth factor receptor; angiogenesis; neovascularization, pathologic; sarcoma; tissue section; statistical significance; fibrosarcoma; microarray analysis; oligonucleotide array sequence analysis; vascular endothelial growth factor; soft tissue sarcoma; gene control; upregulation; dna microarray; enzyme-linked immunosorbent assay; cancer classification; leiomyosarcoma; fibroblast growth factors; angiopoietin 2; gelatinase a; notch4 receptor; trunk; angiopoietin-2; basic fibroblast growth factor |
| Journal Title: | Journal of Surgical Research |
| Volume: | 135 |
| Issue: | 2 |
| ISSN: | 0022-4804 |
| Publisher: | Academic Press Inc., Elsevier Science |
| Date Published: | 2006-10-01 |
| Start Page: | 282 |
| End Page: | 290 |
| Language: | English |
| DOI: | 10.1016/j.jss.2006.01.023 |
| PUBMED: | 16603191 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 19" - "Export Date: 4 June 2012" - "CODEN: JSGRA" - "Source: Scopus" |
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