Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids

综合和比较基因组分析确定了临床相关的肺类癌组并揭示了超类癌

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作者:N Alcala, N Leblay, A A G Gabriel, L Mangiante, D Hervas, T Giffon, A S Sertier, A Ferrari, J Derks, A Ghantous, T M Delhomme, A Chabrier, C Cuenin, B Abedi-Ardekani, A Boland, R Olaso, V Meyer, J Altmuller, F Le Calvez-Kelm, G Durand, C Voegele, S Boyault, L Moonen, N Lemaitre, P Lorimier, A C Toff

Abstract

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.

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