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

Nat Commun. 2019 Aug 20;10(1):3407. doi: 10.1038/s41467-019-11276-9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Carcinoid Tumor / genetics*
  • Carcinoid Tumor / mortality
  • Carcinoid Tumor / pathology
  • Carcinoma, Large Cell / genetics*
  • Carcinoma, Large Cell / mortality
  • Carcinoma, Large Cell / pathology
  • Comparative Genomic Hybridization
  • Datasets as Topic
  • Female
  • Genomics
  • Homeodomain Proteins / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Lung / pathology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Machine Learning
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Prognosis
  • Small Cell Lung Carcinoma / genetics*
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / pathology
  • Survival Rate
  • Young Adult

Substances

  • Biomarkers, Tumor
  • DLL3 protein, human
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • OTP protein, human