Article

Expression of endothelin-1 is related to poor prognosis in non-small cell lung carcinoma.

Department of Surgery, University of Pisa, 56100 Pisa, Italy.
European Journal of Cancer (impact factor: 5.54). 12/2005; 41(18):2828-35. DOI:10.1016/j.ejca.2005.08.030 pp.2828-35
Source: PubMed

ABSTRACT The endothelin (ET) system influences tumourigenesis and tumour progression by various mechanisms, including angiogenesis. The aim of this study was to determine whether the expression of endothelin-1 (ET-1) is related to the angiogenic phenomenon in lung cancer and whether it could be involved in its clinical behaviour. Expression of ET-1, endothelin-converting enzyme-1 (ECE-1) and endothelin-receptors ETA and ETB was examined in 201 non-small cell lung carcinoma (NSCLC) and corresponding normal tissues using real-time polymerase chain reaction (RT-PCR). Forty NSCLC were also analysed for vascular endothelial growth factor (VEGF) expression by a competitive-PCR approach to assess whether ET-1 expression was related to this angiogenic factor. A higher number of cases with ET-1, ECE-1 and ETA mRNA expression was observed in malignant lung tumours compared with normal lung tissues (45.7% versus 33% for ET-1 (P < 0.0001); 38.3% versus 16.5% for ECE-1 (P = 0.004); and 42.8% versus 28.5% for ETA (P < 0.0001)). On the other hand, ETB mRNA was higher in normal lung tissues than in tumour samples (58.5% versus 52.8% (P < 0.0001)). Immunohistochemical analysis was also performed in 78 cases, selected from among those with high ET-1 mRNA, to confirm the presence of ET-1 protein and to determine its distribution and localisation. Moreover, an interesting relationship was observed between ET-1 and VEGF mRNA levels (P = 0.02). At univariate analysis, clinical-pathological parameters, such as sex, nodal metastatic involvement and stage, and ET-1 expression were seen to be significant predictors of worse prognosis regarding both overall survival (P = 0.001, P = 0.0003, P = 0.001 and P = 0.03, respectively) and disease-free interval (P = 0.0005, P = 0.0007, P = 0.001 and P = 0.04, respectively). We conclude that ET-1 could be involved in angiogenic phenomena in NSCLC and may represent a further indicator of progression and poor prognosis in this type of cancer, with interesting therapeutic implications.

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    Article: Large-scale analysis of network bistability for human cancers.
    Tetsuya Shiraishi, Shinako Matsuyama, Hiroaki Kitano
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    ABSTRACT: Protein-protein interaction and gene regulatory networks are likely to be locked in a state corresponding to a disease by the behavior of one or more bistable circuits exhibiting switch-like behavior. Sets of genes could be over-expressed or repressed when anomalies due to disease appear, and the circuits responsible for this over- or under-expression might persist for as long as the disease state continues. This paper shows how a large-scale analysis of network bistability for various human cancers can identify genes that can potentially serve as drug targets or diagnosis biomarkers.
    PLoS Computational Biology 01/2010; 6(7):e1000851. · 5.22 Impact Factor
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Keywords

clinical behaviour
 
clinical-pathological parameters
 
competitive-PCR approach
 
endothelin-converting enzyme-1
 
endothelin-receptors ETA
 
ET-1 expression
 
ET-1 mRNA
 
ETA mRNA expression
 
ETB mRNA
 
interesting relationship
 
interesting therapeutic implications
 
lung cancer
 
malignant lung tumours
 
nodal metastatic involvement
 
poor prognosis
 
tumour progression
 
tumour samples
 
univariate analysis
 
VEGF mRNA levels
 
worse prognosis