Neurotensin Receptor 1 Determines the Outcome of Non-Small Cell Lung Cancer
Neurotensin Receptor 1 Determines the Outcome of Non-Small Cell Lung Cancer
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DOI：
10.1158/1078-0432.ccr-10-0659
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发表时间：
2010-09-01
影响因子：
11.5
通讯作者：
Forgez, Patricia
中科院分区：
文献类型：
--
作者：
Alifano, Marco;Souaze, Frederique;Forgez, Patricia
目的：本研究旨在探讨神经降压素/神经降压素受体I（NTSR 1）复合物在非小细胞肺癌（NSCLC）progression.Experimental Design的作用：神经降压素和NTSR 1的表达进行了研究转录组分析和免疫组化在两个系列的74和139连续患者的病理I期NSCLC腺癌。结果与临床病理特征相关。实验肿瘤是从恶性人肺癌细胞系A459和LNM 35的亚克隆LNM-R产生的。通过小发夹RNA介导的NTSR 1和neurotensin.Results沉默研究了神经降压素信号系统在肿瘤生长和转移中的作用：在一系列的74例患者中进行的转录组分析表明，NTSR 1的正调控使其进入与无复发生存相关的前50个基因。免疫组化结果显示，神经降压素和NTSR 1阳性染色分别在60.4%和59.7%的肺腺癌。在单因素分析中，NTSR 1表达与较差的5年总生存率（P = 0.0081）和无复发生存率（P = 0.0024）密切相关。多因素分析显示，年龄≥ 65岁（P = 0.0018）和NTSR 1表达（P = 0.0034）是独立的负性预后因素。实验肿瘤异种移植产生的神经降压素和NTSR 1沉默的人肺癌细胞显示，神经降压素增强原发性肿瘤的生长和生产的大规模淋巴结转移通过自分泌和旁分泌regulation loop.Conclusion：NTSR 1表达被确定为一个潜在的新的预后生物标志物手术切除的I期肺腺癌，作为NTSR 1激活被证明参与肺癌的进展。临床癌症研究; 16（17）; 4401-10。(C)2010年AACR。
Purpose: This study aimed to investigate the role of the neurotensin/neurotensin receptor I (NTSR1) complex in non-small cell lung cancer (NSCLC) progression.Experimental Design: The expression of neurotensin and NTSR1 was studied by transcriptome analysis and immunohistochemistry in two series of 74 and 139 consecutive patients with pathologic stage I NSCLC adenocarcinoma. The findings were correlated with clinic-pathologic features. Experimental tumors were generated from the malignant human lung carcinoma cell line A459, and a subclone of LNM35, LNM-R. The role of the neurotensin signaling system on tumor growth and metastasis was investigated by small hairpin RNA-mediated silencing of NTSR1 and neurotensin.Results: Transcriptome analysis carried out in a series of 74 patients showed that the positive regulation of NTSR1 put it within the top 50 genes related with relapse-free survival. Immunohistochemistry revealed neurotensin-and NTSR1-positive staining in 60.4% and 59.7% of lung adenocarcinomas, respectively. At univariate analysis, NTSR1 expression was strongly associated with worse 5-year overall survival rate (P = 0.0081) and relapse-free survival (P = 0.0024). Multivariate analysis showed that patients over 65 years of age (P = 0.0018) and NTSR1 expression (P = 0.0034) were independent negative prognostic factors. Experimental tumor xenografts generated by neurotensin-and NTSR1-silenced human lung cancer cells revealed that neurotensin enhanced primary tumor growth and production of massive nodal metastasis via autocrine and paracrine regulation loops.Conclusion: NTSR1 expression was identified as a potential new prognostic biomarker for surgically resected stage I lung adenocarcinomas, as NTSR1 activation was shown to participate in lung cancer progression. Clin Cancer Res; 16(17); 4401-10. (C) 2010 AACR.