title: Neurotensin receptor 1 determines the outcome of non-small cell lung cancer.
abstract: OBJECTIVE
  This study aimed to investigate the role of the neurotensin/neurotensin receptor I (NTSR1) complex in non-small cell lung cancer (NSCLC) progression.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Service de chirurgie thoracique, Hôtel-Dieu, Paris, France.
authors.forename: Marco
authors.initials: M
authors.lastname: Alifano
authors.forename: Frédérique
authors.initials: F
authors.lastname: Souazé
authors.forename: Sandra
authors.initials: S
authors.lastname: Dupouy
authors.forename: Sophie
authors.initials: S
authors.lastname: Camilleri-Broët
authors.forename: Mohamad
authors.initials: M
authors.lastname: Younes
authors.forename: Sadi-Menad
authors.initials: SM
authors.lastname: Ahmed-Zaïd
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cancellieri
authors.forename: Stefania
authors.initials: S
authors.lastname: Damiani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Boaron
authors.forename: Philippe
authors.initials: P
authors.lastname: Broët
authors.forename: Lance D
authors.initials: LD
authors.lastname: Miller
authors.forename: Christian
authors.initials: C
authors.lastname: Gespach
authors.forename: Jean François
authors.initials: JF
authors.lastname: Regnard
authors.forename: Patricia
authors.initials: P
authors.lastname: Forgez
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D015999:Multivariate Analysis; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009496:Neurotensin / Q000235:genetics* / Q000378:metabolism; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D034622:RNA Interference; D018028:Receptors, Neurotensin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D009496:Neurotensin