Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids.
Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Carcinoid Tumor
/ genetics
Carcinoma, Large Cell
/ genetics
Comparative Genomic Hybridization
Datasets as Topic
Female
Genomics
Homeodomain Proteins
/ genetics
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Lung
/ pathology
Lung Neoplasms
/ genetics
Machine Learning
Male
Membrane Proteins
/ genetics
Middle Aged
Nerve Tissue Proteins
/ genetics
Prognosis
Small Cell Lung Carcinoma
/ genetics
Survival Rate
Young Adult
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 08 2019
20 08 2019
Historique:
received:
07
11
2018
accepted:
02
07
2019
entrez:
22
8
2019
pubmed:
23
8
2019
medline:
30
11
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31431620
doi: 10.1038/s41467-019-11276-9
pii: 10.1038/s41467-019-11276-9
pmc: PMC6702229
doi:
Substances chimiques
Biomarkers, Tumor
0
DLL3 protein, human
0
Homeodomain Proteins
0
Intracellular Signaling Peptides and Proteins
0
Membrane Proteins
0
Nerve Tissue Proteins
0
OTP protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3407Subventions
Organisme : World Health Organization
ID : 001
Pays : International
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