Dkk-3 expression in the tumor endothelium: a novel prognostic marker of pancreatic adenocarcinomas.
Cancer Sci
; 100(8): 1414-20, 2009 Aug.
Article
em En
| MEDLINE
| ID: mdl-19493271
ABSTRACT
Dkk-3 is proposed to be a new specific marker for tumor endothelial cells. Here we analyzed the clinical relevance of Dkk-3 expression in pancreas adenocarcinomas and determined its role on endothelial cell growth in vitro. Microvessel density in tumor samples was immunohistochemically determined using Dkk-3 and CD31 as endothelial cell markers, respectively. Based on the median microvessel density as a cut-off point, patients were categorized into high and low microvessel density groups and a correlation with survival and clinical parameters was assessed. Moreover, the role of Dkk-3 expression on chemosensitivity of endothelial cells was analyzed. In contrast to CD31 staining, Dkk-3-positive vessels were found only in tumor tissue and Dkk-3 microvessel density significantly correlated negative with tumor grading. In survival analysis the median survival time was 7 months for patients with Dkk-3 low, and 15 months for Dkk-3 high microvessel density (P = 0.0013). Subset analysis of patients receiving gemcitabine therapy showed that overall survival was significantly decreased in Dkk-3 low tumors than in high tumors (P = 0.009). In Cox regression Dkk-3 emerged as a significant independent parameter (P = 0.024). Dkk-3 overexpression in endothelial cells resulted in significantly enhanced growth inhibition after 5-fluorouracil or gemcitabine treatment compared to control endothelial cells and cancer cell lines. Dkk-3 low microvessel density was associated with tumor progression and worse clinical outcome. Overexpression of Dkk-3 enhanced endothelial cell growth inhibition to chemotherapeutic drugs. Therefore, we suggest that Dkk-3 high microvessel density may help to select patients who may benefit from chemotherapy.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Adenocarcinoma
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Biomarcadores Tumorais
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Peptídeos e Proteínas de Sinalização Intercelular
/
Endotélio
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cancer Sci
Ano de publicação:
2009
Tipo de documento:
Article