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Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer

Author

Listed:
  • Verena Jabs
  • Karolina Edlund
  • Helena König
  • Marianna Grinberg
  • Katrin Madjar
  • Jörg Rahnenführer
  • Simon Ekman
  • Michael Bergkvist
  • Lars Holmberg
  • Katja Ickstadt
  • Johan Botling
  • Jan G Hengstler
  • Patrick Micke

Abstract

Non-small cell lung cancer (NSCLC) represents a genomically unstable cancer type with extensive copy number aberrations. The relationship of gene copy number alterations and subsequent mRNA levels has only fragmentarily been described. The aim of this study was to conduct a genome-wide analysis of gene copy number gains and corresponding gene expression levels in a clinically well annotated NSCLC patient cohort (n = 190) and their association with survival. While more than half of all analyzed gene copy number-gene expression pairs showed statistically significant correlations (10,296 of 18,756 genes), high correlations, with a correlation coefficient >0.7, were obtained only in a subset of 301 genes (1.6%), including KRAS, EGFR and MDM2. Higher correlation coefficients were associated with higher copy number and expression levels. Strong correlations were frequently based on few tumors with high copy number gains and correspondingly increased mRNA expression. Among the highly correlating genes, GO groups associated with posttranslational protein modifications were particularly frequent, including ubiquitination and neddylation. In a meta-analysis including 1,779 patients we found that survival associated genes were overrepresented among highly correlating genes (61 of the 301 highly correlating genes, FDR adjusted p

Suggested Citation

  • Verena Jabs & Karolina Edlund & Helena König & Marianna Grinberg & Katrin Madjar & Jörg Rahnenführer & Simon Ekman & Michael Bergkvist & Lars Holmberg & Katja Ickstadt & Johan Botling & Jan G Hengstle, 2017. "Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer," PLOS ONE, Public Library of Science, vol. 12(11), pages 1-23, November.
    • Handle: RePEc:plo:pone00:0187246
    DOI: 10.1371/journal.pone.0187246
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    1. Andrea H. Bild & Guang Yao & Jeffrey T. Chang & Quanli Wang & Anil Potti & Dawn Chasse & Mary-Beth Joshi & David Harpole & Johnathan M. Lancaster & Andrew Berchuck & John A. Olson & Jeffrey R. Marks &, 2006. "Oncogenic pathway signatures in human cancers as a guide to targeted therapies," Nature, Nature, vol. 439(7074), pages 353-357, January.
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