Virtual Library

Start Your Search

K.J. Craddock



Author of

  • +

    P2.01 - Poster Session with Presenters Present (ID 461)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
    • +

      P2.01-015 - Differentially Expressed microRNAs in Lung Adenocarcinoma Invert Effects of Copy Number Aberrations of Prognostic Genes (ID 4771)

      14:30 - 14:30  |  Author(s): K.J. Craddock

      • Abstract

      Background:
      Across multiple cancer histologies, many significantly down-regulated genes reside within chromosomal regions with increased number of copies, and vice versa. These “paradoxical genes” have been usually ignored as a noise, but could be a consequence of epigenetic regulatory mechanisms, including microRNA-mediated control of mRNA transcription.

      Methods:
      To identify paradoxical genes in lung adenocarcinoma (LUAD) we curated and analyzed gene expression and copy number aberrations across 1,064 LUAD samples, including newly-generated aCGH data from 65 samples. We then analyzed 9 LUAD microRNA expression studies to compile a list of consistently deregulated microRNAs. Finally, using microRNA:gene networks from mirDIP we examined possible association between microRNAs and paradoxical genes.

      Results:
      We identified 85 genes whose differential expression consistently contrasts the aberrations of their copy numbers. 70 genes were validated using TCGA-LUAD data. We showed that paradoxical expression of these genes is associated with 19 microRNAs, whose significant deregulation in LUAD has been consistently reported. Importantly, these genes form a clinically significant prognostic signature.Figure 1Figure 2





      Conclusion:
      Paradoxical gene expression, caused by microRNA deregulation, is preserved across patient cohorts, and forms a prognostic LUAD signature.