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Diagnostic markers that distinguish colon and ovarian adenocarcinomas: identification by genomic, proteomic, and tissue array profiling

  1. Author:
    Nishizuka, S.
    Chen, S. T.
    Gwadry, F. G.
    Alexander, J.
    Major, S. M.
    Scherf, U.
    Reinhold, W. C.
    Waltham, M.
    Charboneau, L.
    Young, L.
    Bussey, K. J.
    Kim, S. Y.
    Lababidi, S.
    Lee, J. K.
    Pittaluga, S.
    Scudiero, D. A.
    Sausville, E. A.
    Munson, P. J.
    Petricoin, E. F.
    Liotta, L. A.
    Hewitt, S. M.
    Raffeld, M.
    Weinstein, J. N.

  2. Author Address

    NCI, Lab Mol Pharmacol, Genom & Bioinformat Grp, NIH, Bldg 37,Rm 5056, Bethesda, MD 20892 USA NCI, Lab Mol Pharmacol, Genom & Bioinformat Grp, NIH, Bethesda, MD 20892 USA Ctr Informat Technol, Math & Stat Comp Lab, Analyt Biostat Sect, NCI, Bethesda, MD 20814 USA Dev Therapeut Program, Div Canc Treatment & Diagnosis, Bethesda, MD 20814 USA Sci Applicat Int Corp, NCI, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA Food & Drug Adm, Ctr Biol Evaluat & Res, Tissue Proteom Unit, Div Therapeut Prot, Bethesda, MD 20814 USA Weinstein JN NCI, Lab Mol Pharmacol, Genom & Bioinformat Grp, NIH, Bldg 37,Rm 5056, Bethesda, MD 20892 USA
    1. Year: 2003
  2. Journal: Cancer Research
    1. 63
    2. 17
    3. Pages: 5243-5250
  4. Type of Article: Article
  1. Abstract:

    Colon and ovarian cancers can be difficult to distinguish in the abdomen, and the distinction is important because it determines which drugs will be used for therapy. To identify molecular markers for that differential diagnosis, we developed a multistep protocol starting with the 60 human cancer cell lines used by the National Cancer Institute to screen for new anticancer agents. The steps included: (a) identification of candidate markers using cDNA microarrays; (b) verification of clone identities by resequencing; (e) corroboration of transcript levels using Affymetrix oligonucleotide chips; (d) quantitation of protein expression by "reverse-phase" protein microarray; and (e) prospective validation of candidate markers on clinical tumor sections in tissue microarrays. The two best candidates identified were villin for colon cancer cells and moesin for ovarian cancer cells. Because moesin stained stromal elements in both types of cancer, it would probably not have been identified as a marker if we had started with mRNA or protein profiling of bulk tumors. Villin appears at least as useful as the currently used colon cancer marker cytokeratin 20, and moesin also appears to have utility. The multistep process introduced here has the potential to produce additional markers for cancer diagnosis, prognosis, and therapy.

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