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Neurotensin Receptor 1 Determines the Outcome of Non-Small Cell Lung Cancer

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.
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Contributor : Frédérique Souazé Connect in order to contact the contributor
Submitted on : Wednesday, January 29, 2020 - 2:42:50 PM
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Marco Alifano, Frédérique Souazé, Sandra Dupouy, Sophie Camilleri-Broët, Mohamad younes, et al.. Neurotensin Receptor 1 Determines the Outcome of Non-Small Cell Lung Cancer. Clinical Cancer Research, American Association for Cancer Research, 2010, 16 (17), pp.4401-4410. ⟨10.1158/1078-0432.CCR-10-0659⟩. ⟨inserm-02459564⟩



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