A Three-Gene Signature for Outcome in Soft Tissue Sarcoma

Purpose: Finding markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens in soft tissue sarcomas is necessary. In this study, we investigated the prognostic values of hypoxia-inducible factor 1...

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Bibliographic Details
Published in:Clinical cancer research 2009-08, Vol.15 (16), p.5191-5198
Main Authors: HOFFMAN, Andreas-Claudius, DANENBERG, Kathleen D, TAUBERT, Helge, DANENBERG, Peter V, WUERL, Peter
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
angiogenesis
Antineoplastic agents
Biological and medical sciences
Dermatology
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
HB-EGF
Heparin-binding EGF-like Growth Factor
HIF1a
HPSE
Humans
Hypoxia-Inducible Factor 1, alpha Subunit - genetics
Intercellular Signaling Peptides and Proteins - genetics
Male
Medical sciences
Middle Aged
Models, Biological
Pharmacology. Drug treatments
Prognosis
Sarcoma - diagnosis
Sarcoma - genetics
Sarcoma - mortality
Sensitivity and Specificity
Survival Analysis
three-gene signature
Tumors of the skin and soft tissue. Premalignant lesions
Vascular Endothelial Growth Factor C - genetics
VEGF-C
Young Adult
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Summary:Purpose: Finding markers or gene sets that would further classify patients into different risk categories and thus allow more individually adapted multimodality treatment regimens in soft tissue sarcomas is necessary. In this study, we investigated the prognostic values of hypoxia-inducible factor 1a ( HIF1a ), heparin-binding epidermal growth factor–like growth factor ( HB-EGF ), vascular endothelial growth factor ( VEGF ), and other angiogenesis-related gene expressions, as well as their interrelationships. Experimental Design: Formalin-fixed paraffin-embedded tissue samples were obtained from 45 patients with soft tissue sarcoma (median age 57 years, range 16–85 years). After laser capture microdissection direct quantitative real-time reverse transcription-PCR (TaqMan) assays were done in triplicates to determine HIF1a, HB-EGF, VEGF , and other gene expression levels. Results: Multivariate Cox regression analysis revealed significant independent associations of HB-EGF, HIF1a , and VEGF-C gene expression to the overall survival ( P < 0.0001). A combined factor of these three genes showed a relative risk for shorter survival of 5.5, more than twice higher as in an increasing International Union against Cancer Stage. Receiver operating characteristic curve analysis showed a significant sensitivity of 73% and specificity of 82% of this factor for the diagnosis of short (
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-08-2534