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    A new 12-gene diagnostic biomarker signature of melanoma revealed by integrated microarray analysis.

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    Publication date
    2013
    Author
    Liu, Wanting
    Peng, Yonghong
    Tobin, Desmond J.
    Keyword
    Diagnostic biomarker signature; Genes and genetics; Melanoma; Integrated microarray analysis; Epidermis; Skin;
    Peer-Reviewed
    yes
    
    Metadata
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    Abstract
    Genome-wide microarray technology has facilitated the systematic discovery of diagnostic biomarkers of cancers and other pathologies. However, meta-analyses of published arrays often uncover significant inconsistencies that hinder advances in clinical practice. Here we present an integrated microarray analysis framework, based on a genome-wide relative significance (GWRS) and genome-wide global significance (GWGS) model. When applied to five microarray datasets on melanoma published between 2000 and 2011, this method revealed a new signature of 200 genes. When these were linked to so-called ‘melanoma driver’ genes involved in MAPK, Ca2+, and WNT signaling pathways we were able to produce a new 12-gene diagnostic biomarker signature for melanoma (i.e., EGFR, FGFR2, FGFR3, IL8, PTPRF, TNC, CXCL13, COL11A1, CHP2, SHC4, PPP2R2C, and WNT4). We have begun to experimentally validate a subset of these genes involved in MAPK signaling at the protein level, including CXCL13, COL11A1, PTPRF and SHC4 and found these to be over-expressed in metastatic and primary melanoma cells in vitro and in situ compared to melanocytes cultured from healthy skin epidermis and normal healthy human skin. While SHC4 has been reported previously to be associated to melanoma, this is the first time CXCL13, COL11A1, and PTPRF have been associated with melanoma on experimental validation. Our computational evaluation indicates that this 12-gene biomarker signature achieves excellent diagnostic power in distinguishing metastatic melanoma from normal skin and benign nevus. Further experimental validation of the role of these 12 genes in a new signaling network may provide new insights into the underlying biological mechanisms driving the progression of melanoma.
    URI
    http://hdl.handle.net/10454/6900
    Version
    No full-text available in the repository
    Citation
    Liu, W., Peng, Y. and Tobin, D. J. (2013) A new 12-gene diagnostic biomarker signature of melanoma revealed by integrated microarray analysis. PeerJ, 1, e49. http://dx.doi.org/10.7717/peerj.49
    Link to publisher’s version
    http://dx.doi.org/10.7717/peerj.49
    Type
    Article
    Collections
    Life Sciences Publications

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