This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Eschrich, S. Articles by Yeatman, T. J. Search for Related Content PubMed PubMed Citation Articles by Eschrich, S. Articles by Yeatman, T. J.

Molecular Staging for Survival Prediction of Colorectal Cancer Patients

From the Departments of Surgery, Pathology, and Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; The Institute for Genomic Research, Rockville; Department of Statistics, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, MD; Department of Biochemistry, George Washington University, Washington, DC; The Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby, Denmark; and Department of Medical Genetics, Biomedicum, Helsinki, Finland

Address reprint requests to Timothy J. Yeatman, MD, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, SRB-2, Tampa, FL 33612; email: yeatman{at}moffitt.usf.edu

PURPOSE: The Dukes' staging system is the gold standard for predicting colorectal cancer prognosis; however, accurate classification of intermediate-stage cases is problematic. We hypothesized that molecular fingerprints could provide more accurate staging and potentially assist in directing adjuvant therapy.

METHODS: A 32,000 cDNA microarray was used to evaluate 78 human colon cancer specimens, and these results were correlated with survival. Molecular classifiers were produced to predict outcome.

RESULTS: Molecular staging, based on 43 core genes, was 90% accurate (93% sensitivity, 84% specificity) in predicting 36-month overall survival in 78 patients. This result was significantly better than Dukes' staging (P = .03878), discriminated patients into significantly different groups by survival time (P < .001, log-rank test), and was significantly different from chance (P < .001, 1,000 permutations). Furthermore, the classifier was able to discriminate a survival difference in an independent test set from Denmark. Molecular staging identifies patient prognosis (as represented by 36-month survival) more accurately than the traditional clinical staging, particularly for intermediate Dukes' stage B and C patients. The classifier was based on a core set of 43 genes, including osteopontin and neuregulin, which have biologic significance for this disease.

CONCLUSION: These data support further evaluation of molecular staging to discriminate good from poor prognosis patients, with the potential to direct adjuvant therapy.

Supported by grants from the National Cancer Institute, Bethesda, MD; also supported by the Biostatistics Core and the Microarray Core at H. Lee Moffitt Cancer Center and services provided by the Research Computing Core, University of South Florida.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

This article has been cited by other articles:

				F. Ginty, S. Adak, A. Can, M. Gerdes, M. Larsen, H. Cline, R. Filkins, Z. Pang, Q. Li, and M. C. Montalto The Relative Distribution of Membranous and Cytoplasmic Met Is a Prognostic Indicator in Stage I and II Colon Cancer Clin. Cancer Res., June 15, 2008; 14(12): 3814 - 3822. [Abstract] [Full Text] [PDF]

				J. C. Montero, R. Rodriguez-Barrueco, A. Ocana, E. Diaz-Rodriguez, A. Esparis-Ogando, and A. Pandiella Neuregulins and Cancer Clin. Cancer Res., June 1, 2008; 14(11): 3237 - 3241. [Abstract] [Full Text] [PDF]

				I Zlobec and A Lugli Prognostic and predictive factors in colorectal cancer J. Clin. Pathol., May 1, 2008; 61(5): 561 - 569. [Abstract] [Full Text] [PDF]

				J. Shao, M.K. Washington, R. Saxena, and H. Sheng Heterozygous disruption of the PTEN promotes intestinal neoplasia in APCmin/+ mouse: roles of osteopontin Carcinogenesis, December 1, 2007; 28(12): 2476 - 2483. [Abstract] [Full Text] [PDF]

				D. N. Hebert and M. Molinari In and Out of the ER: Protein Folding, Quality Control, Degradation, and Related Human Diseases Physiol Rev, October 1, 2007; 87(4): 1377 - 1408. [Abstract] [Full Text] [PDF]

				A. Barrier, P.-Y. Boelle, S. Houry, S. Dudoit, and A. Lemoine In Reply J. Clin. Oncol., July 1, 2007; 25(19): 2862 - 2863. [Full Text] [PDF]

				J. Quackenbush Extracting biology from high-dimensional biological data J. Exp. Biol., May 1, 2007; 210(9): 1507 - 1517. [Abstract] [Full Text] [PDF]

				M. F.G. de Maat, N. Umetani, E. Sunami, R. R. Turner, and D. S.B. Hoon Assessment of Methylation Events during Colorectal Tumor Progression by Absolute Quantitative Analysis of Methylated Alleles Mol. Cancer Res., May 1, 2007; 5(5): 461 - 471. [Abstract] [Full Text] [PDF]

				E. H. Jensen, J. M. Lewis, J. M. McLoughlin, M. D. Alvarado, A. Daud, J. Messina, S. Enkemann, T. J. Yeatman, V. K. Sondak, and A. I. Riker Down-Regulation of Pro-Apoptotic Genes is an Early Event in the Progression of Malignant Melanoma Ann. Surg. Oncol., April 1, 2007; 14(4): 1416 - 1423. [Abstract] [Full Text] [PDF]

				M. Del Rio, F. Molina, C. Bascoul-Mollevi, V. Copois, F. Bibeau, P. Chalbos, C. Bareil, A. Kramar, N. Salvetat, C. Fraslon, et al. Gene Expression Signature in Advanced Colorectal Cancer Patients Select Drugs and Response for the Use of Leucovorin, Fluorouracil, and Irinotecan J. Clin. Oncol., March 1, 2007; 25(7): 773 - 780. [Abstract] [Full Text] [PDF]

				Y.-H. Lin, J. Friederichs, M. A. Black, J. Mages, R. Rosenberg, P. J. Guilford, V. Phillips, M. Thompson-Fawcett, N. Kasabov, T. Toro, et al. Multiple Gene Expression Classifiers from Different Array Platforms Predict Poor Prognosis of Colorectal Cancer Clin. Cancer Res., January 15, 2007; 13(2): 498 - 507. [Abstract] [Full Text] [PDF]

				V. A. Valera, B. A. Walter, N. Yokoyama, Y. Koyama, T. Iiai, H. Okamoto, and K. Hatakeyama Prognostic Groups in Colorectal Carcinoma Patients Based on Tumor Cell Proliferation and Classification and Regression Tree (CART) Survival Analysis Ann. Surg. Oncol., January 1, 2007; 14(1): 34 - 40. [Abstract] [Full Text] [PDF]

				M. Bloomston, E. C. Ellison, P. Muscarella, O. Al-Saif, E. W. Martin, W. S. Melvin, and W. L. Frankel Stromal Osteonectin Overexpression Is Associated with Poor Outcome in Patients with Ampullary Cancer Ann. Surg. Oncol., January 1, 2007; 14(1): 211 - 217. [Abstract] [Full Text] [PDF]

				J. Quackenbush Microarray analysis and tumor classification. N. Engl. J. Med., June 8, 2006; 354(23): 2463 - 2472. [Full Text] [PDF]