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Kenneth J. Craddock

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    P3.03 - Biology (Not CME Accredited Session) (ID 969)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.03-06 - Differentially Expressed microRNAs in Lung Adenocarcinoma Invert Effects of Copy Number Aberrations of Prognostic Genes (ID 14319)

      12:00 - 13:30  |  Author(s): Kenneth J. Craddock

      • Abstract


      Significant associations between chromosomal copy number aberrations (CNAs) and differential gene expression have been found across many cancers. However, significantly downregulated genes have been often found to reside within chromosomal regions with increased number of copies and vice versa, creating a paradoxical signal. This phenomenon was usually ignored as a noise, but can potentially be a consequence of interference of other regulatory mechanisms controlling mRNA transcription.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      To explore existence of such paradoxes in lung adenocarcinoma (LUAD), we performed integrative analysis of 1,937 tumour and normal tissue samples, comprising copy number aberrations, gene expression and microRNA expressions data and conducted meta-analysis of 9 microRNA expression studies.

      4c3880bb027f159e801041b1021e88e8 Result

      We identified and validated 75 “paradoxical” genes whose differential expression consistently contrasted with aberrations of their copy numbers. Of these, 41 genes (p < 0.001) are prognostic and form a clinically relevant signature. Interestingly, differential expression of 19 microRNAs that are frequently deregulated in LUAD, explains observed paradoxes.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results show that deregulation of paradoxical genes is crucial in LUAD and their expression pattern is maintained epigenetically, defying gene copy number status. Our work highlights importance of large integrative analysis of diverse biological data and the need to examine phenomena that contrast the established knowledge.