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Supervised analyses comparing patients with distant metastases versus primary tumors or regional metastases showed that the distant metastases were distinct and distinguished by the lack of expression of fibroblast\/mesenchymal genes, and by the high expression of a 13-gene profile (that is, the 'vascular endothelial growth factor (VEGF) profile') that included<jats:italic>VEGF, ANGPTL4, ADM<\/jats:italic>and the monocarboxylic acid transporter<jats:italic>SLC16A3<\/jats:italic>. At least 8 out of 13 of these genes contained HIF1\u03b1 binding sites, many are known to be HIF1\u03b1-regulated, and expression of the VEGF profile correlated with HIF1\u03b1 IHC positivity. The VEGF profile also showed prognostic significance on tests of sets of patients with breast and lung cancer and glioblastomas, and was an independent predictor of outcomes in primary breast cancers when tested in models that contained other prognostic gene expression profiles and clinical variables.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data identify a compact<jats:italic>in vivo<\/jats:italic>hypoxia signature that tends to be present in distant metastasis samples, and which portends a poor outcome in multiple tumor types.<\/jats:p><jats:p>This signature suggests that the response to hypoxia includes the ability to promote new blood and lymphatic vessel formation, and that the dual targeting of multiple cell types and pathways will be needed to prevent metastatic spread.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1741-7015-7-9","type":"journal-article","created":{"date-parts":[[2009,4,21]],"date-time":"2009-04-21T18:14:18Z","timestamp":1240337658000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":147,"title":["A compact VEGF signature associated with distant metastases and poor outcomes"],"prefix":"10.1186","volume":"7","author":[{"given":"Zhiyuan","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chad","family":"Livasy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaping","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel S","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew G","family":"Ewend","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A","family":"Carey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subbaya","family":"Subramanian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"West","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Ikpatt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olufunmilayo I","family":"Olopade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt","family":"van de Rijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles M","family":"Perou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,3,16]]},"reference":[{"issue":"6900","key":"187_CR1","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/418823a","volume":"418","author":"R Bernards","year":"2002","unstructured":"Bernards R, Weinberg RA: A progression puzzle. 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