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[Cancer Research 63, 5243-5250, September 1, 2003]
© 2003 American Association for Cancer Research

Regular Articles

Diagnostic Markers That Distinguish Colon and Ovarian Adenocarcinomas

Identification by Genomic, Proteomic, and Tissue Array Profiling

Satoshi Nishizuka, Sing-Tsung Chen1, Fuad G. Gwadry2, Jes Alexander3, Sylvia M. Major, Uwe Scherf2, William C. Reinhold, Mark Waltham4, Lu Charboneau, Lynn Young, Kimberly J. Bussey, Sohyoung Kim, Samir Lababidi, Jae K. Lee5, Stefania Pittaluga, Dominic A. Scudiero, Edward A. Sausville, Peter J. Munson, Emmanuel F. Petricoin, III, Lance A. Liotta, Stephen M. Hewitt, Mark Raffeld and John N. Weinstein6

Genomics and Bioinformatics Group, Laboratory of Molecular Pharmacology [S. N., F. G. G., J. A., S. M. M., U. S., W. C. R., M. W., K. J. B., S. K., S. L., J. K. L., J. N. W.], Laboratory of Pathology [S-T. C., L. C., S. P., L. A. L., S. M. H., M. R.], Office of the Associate Director, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis [E. A. S.], National Cancer Institute, Analytical Biostatistics Section, Mathematical and Statistical Computing Laboratory, Center for Information Technology [L. Y., P. J. M.], NIH, Bethesda, Maryland 20814; Science Applications International Corporation-Frederick-National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702 [D. A. S.]; and Tissue Proteomics Unit, Division of Therapeutic Proteins, Center for Biological Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20814 [E. F. P.]

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; (c) 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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Copyright © 2003 by the American Association for Cancer Research.