Journal Article

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

Su, Zhen, Du, Zhou, Fei, Teng, Brown, Myles, Liu, X Shirley, Verhaak, Roel G W, Chen, Yiwen, Zhang, Yong

2013

Overview

By integrating the expression profiles of long noncoding RNAs (lncRNAs) with clinical outcome and somatic copy-number alteration, the authors identified new lncRNAs that are associated with certain cancer subtypes and clinical prognoses. Experimental validation of the prostate cancer cell growth dependence of two new lncRNAs demonstrates the power of this approach for discovering disease-related lncRNAs. 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.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/114 / 631/337/384/2568 / 631/67 / 692/699 / Adenocarcinoma - genetics / Adenocarcinoma - pathology / Amino Acid Sequence / Biochemistry / Biological Microscopy / Biomarkers, Tumor / Biomedical research / Cancer / Cell Line, Tumor - chemistry / Conserved Sequence / DNA Probes / DNA, Intergenic / Exons / Gene Dosage / Gene Expression Profiling - methods / Gene Expression Regulation, Neoplastic - genetics / Genes, Overlapping / Genetic aspects / Genomics / Humans / Introns / Kaplan-Meier Estimate / Life Sciences / Male / Membrane Biology / Models, Molecular / Molecular biology / Molecular Sequence Data / Molecular Targeted Therapy / Neoplasms - classification / Neoplasms - genetics / Neoplasms - mortality / Oligonucleotide Array Sequence Analysis / Physiological aspects / Physiology / Probes / Prognosis / Prostate cancer / Prostatic Neoplasms - genetics / Prostatic Neoplasms - pathology / Protein Conformation / Protein Structure / resource / Ribonucleic acid / RNA / RNA, Long Noncoding - analysis / RNA, Long Noncoding - classification / RNA, Long Noncoding - genetics / RNA, Neoplasm - analysis / RNA, Neoplasm - genetics / RNA-protein interactions / Sequence Alignment / Sequence Homology, Amino Acid