1. Neurotensin Receptor 1 Determines the Outcome of Non-Small Cell Lung Cancer
- Author
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Sandra Dupouy, Lance D. Miller, Philippe Broët, Stefania Damiani, Christian Gespach, Mohamad Younes, Patricia Forgez, Marco Alifano, Sophie Camilleri-Broët, Frédérique Souazé, Alessandra Cancellieri, Maurizio Boaron, Sadi-Menad Ahmed-Zaïd, Jean-François Regnard, Takashi Takahashi, Service de chirurgie thoracique [Hôtel-Dieu], Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biomarqueurs prédictifs de la progression des metaplasies et dysplasies des epitheliums (Biométadys), Université de Nantes (UN), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Méthodologie biostatistique de la génomique fonctionnelle en épidémiologie clinique (JE2492), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Center for Neurological Diseases and Cancer [Nagoya], Maggiore-Bellaria Hospital [Bologna], Wake Forest University, Souazé, Frédérique, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Alifano M., Souazé F., Dupouy S., Camilleri-Broët S., Younes M., Ahmed-Zaïd S.M., Takahashi T., Cancellieri A., Damiani S., Boaron M., Broët P., Miller L.D., Gespach C., Regnard J.F., and Forgez P.
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Male ,Cancer Research ,Pathology ,Lung Neoplasms ,[SDV]Life Sciences [q-bio] ,Kaplan-Meier Estimate ,Metastasis ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Outcome Assessment, Health Care ,Receptors, Neurotensin ,Neurotensin receptor ,0303 health sciences ,Reverse Transcriptase Polymerase Chain Reaction ,Middle Aged ,Prognosis ,Immunohistochemistry ,Primary tumor ,3. Good health ,[SDV] Life Sciences [q-bio] ,NON SMALL CELL CANCER ,Oncology ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Female ,RNA Interference ,medicine.medical_specialty ,Neurotensin receptor 1 ,Transplantation, Heterologous ,Mice, Nude ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Lung cancer ,Aged ,030304 developmental biology ,business.industry ,Gene Expression Profiling ,Cancer ,Neoplasms, Experimental ,medicine.disease ,NEUROTENSIN ,chemistry ,Multivariate Analysis ,Cancer research ,business ,LUNG ,Neurotensin - Abstract
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. ©2010 AACR.
- Published
- 2010
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