Expression of endothelia-1 is related to poor prognosis in non-small cell lung carcinoma
Expression of endothelia-1 is related to poor prognosis in non-small cell lung carcinoma
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DOI：
10.1016/j.ejca.2005.08.030
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发表时间：
2005-12-01
影响因子：
8.4
通讯作者：
Fontanini, G
中科院分区：
文献类型：
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作者：
Boldrini, L;Gisfredi, S;Fontanini, G
内皮素（ET）系统通过多种机制影响肿瘤发生和肿瘤进展，包括血管生成。本研究旨在探讨内皮素-1（ET-1）的表达与肺癌血管生成的关系及其与肺癌临床行为的关系。应用实时荧光定量聚合酶链反应（RT-PCR）检测了201例非小细胞肺癌（NSCLC）组织及相应正常肺组织中内皮素（ET-1）、内皮素转换酶（ECE-1）及内皮素受体（ETA）和内皮素受体（ETB）的表达。还通过竞争性PCR方法分析了40例NSCLC的血管内皮生长因子（VEGF）表达，以评估ET-1表达是否与该血管生成因子相关。恶性肺肿瘤组织中ET-1、ECE-1和ETA mRNA的表达率分别为45.7%和33%（P <0.0001），38.3%和16.5%（P = 0.004），42.8%和28.5%（P <0.0001）。另一方面，ETB mRNA在正常肺组织中高于肿瘤样品（58.5%比52.8%（P <0.0001））。免疫组化分析也进行了78例，从那些高ET-1 mRNA中选出，以确认ET-1蛋白的存在，并确定其分布和定位。ET-1和VEGF mRNA表达水平之间存在显著相关性（P = 0.02）。在单因素分析中，临床病理参数，如性别，淋巴结转移和分期，ET-1表达被认为是总生存率和预后不良的重要预测因素。（分别为P = 0.001、P = 0.0003、P = 0.001和P = 0.03）和无病间期（分别为P = 0.0005、P = 0.0007、P = 0.001和P = 0.04）。我们得出结论，ET-1可能参与非小细胞肺癌的血管生成现象，并可能代表这种类型的癌症的进展和预后不良的进一步指标，具有有趣的治疗意义。(c)2005爱思唯尔有限公司保留所有权利。
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, endothelia-converting enzyme-1 (ECE-1) and endothelia-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. (c) 2005 Elsevier Ltd. All rights reserved.