Integrative genomic analyses reveal clinically relevant long noncoding RNAs in human cancer

Nat Struct Mol Biol. 2013 Jul;20(7):908-13. doi: 10.1038/nsmb.2591. Epub 2013 Jun 2.

Abstract

Despite growing appreciation of the importance of long noncoding RNAs (lncRNAs) in normal physiology and disease, our knowledge of cancer-related lncRNAs remains limited. By repurposing microarray probes, we constructed expression profiles of 10,207 lncRNA genes in approximately 1,300 tumors over four different cancer types. Through integrative analysis of the lncRNA expression profiles with clinical outcome and somatic copy-number alterations, we identified lncRNAs that are associated with cancer subtypes and clinical prognosis and predicted those that are potential drivers of cancer progression. We validated our predictions by experimentally confirming prostate cancer cell growth dependence on two newly identified lncRNAs. Our analysis provides a resource of clinically relevant lncRNAs for the development of lncRNA biomarkers and the identification of lncRNA therapeutic targets. It also demonstrates the power of integrating publically available genomic data sets and clinical information for discovering disease-associated lncRNAs.

Publication types

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

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Amino Acid Sequence
  • Biomarkers, Tumor
  • Cell Line, Tumor / chemistry
  • Conserved Sequence
  • DNA Probes
  • DNA, Intergenic
  • Exons
  • Gene Dosage
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic / genetics
  • Genes, Overlapping
  • Humans
  • Introns
  • Kaplan-Meier Estimate
  • Male
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Targeted Therapy
  • Neoplasms / classification
  • Neoplasms / genetics*
  • Neoplasms / mortality
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Protein Conformation
  • RNA, Long Noncoding / analysis
  • RNA, Long Noncoding / classification
  • RNA, Long Noncoding / genetics*
  • RNA, Neoplasm / analysis
  • RNA, Neoplasm / genetics*
  • Sequence Alignment
  • Sequence Homology, Amino Acid

Substances

  • Biomarkers, Tumor
  • DNA Probes
  • DNA, Intergenic
  • RNA, Long Noncoding
  • RNA, Neoplasm