Originally published as JCO Early Release 10.1200/JCO.2004.08.186 on March 29 2004

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 Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, Y. Articles by Atkins, D. Search for Related Content PubMed PubMed Citation Articles by Wang, Y. Articles by Atkins, D.

Gene Expression Profiles and Molecular Markers To Predict Recurrence of Dukes' B Colon Cancer

From Veridex, LLC, a Johnson & Johnson Company, San Diego, CA; and the Departments of Medicine and Surgery, Washington University School of Medicine, St Louis, MO

Address reprint requests to Yixin Wang, Veridex, LLC, a Johnson & Johnson Company, 3210 Merryfield Row, San Diego, CA 92121; e-mail: ywang44{at}vrxus.jnj.com

PURPOSE: The 5-year survival rate of patients with Dukes' B colon cancer is approximately 75%. Identification of the patients at high risk of recurrence in this group would allow better staging and more informed use of adjuvant chemotherapy. In this study, we used DNA chip technology to systematically identify new prognostic markers for tumor relapse in Dukes' B patients.

PATIENTS AND METHODS: Using Affymetrix U133a GeneChip containing approximately 22,000 transcripts (Affymetrix, Santa Clara, CA), RNA samples from 74 patients with Dukes' B colon cancer were analyzed. Thirty-one patients developed tumor relapse in less than 3 years, whereas 43 patients remained disease-free for more than 3 years after surgery. Two supervised class prediction approaches were used to identify gene markers that can best discriminate between patients who would experience relapse and patients who would remain disease-free. A multivariate Cox model was built to predict recurrence.

RESULTS: Gene expression profiling identified a 23-gene signature that predicts recurrence in Dukes'B patients. This signature was validated in 36 independent patients. The overall performance accuracy was 78%. Thirteen of 18 relapse patients and 15 of 18 disease-free patients were predicted correctly, giving an odds ratio of 13 (95% CI, 2.6 to 65; P = .003). The log-rank test indicated a significant difference in disease-free time between the predicted relapse and disease-free patients (P = .0001).

CONCLUSION: The clinical value of these markers is that the patients at a high predicted risk of relapse (13-fold risk) could be upstaged to receive adjuvant therapy, similar to Dukes' C patients. Our data highlight the feasibility of a prognostic assay that could focus more intensive treatment for localized colon cancer.

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

This article has been cited by other articles:

				O. Galamb, F. Sipos, N. Solymosi, S. Spisak, T. Krenacs, K. Toth, Z. Tulassay, and B. Molnar Diagnostic mRNA Expression Patterns of Inflamed, Benign, and Malignant Colorectal Biopsy Specimen and their Correlation with Peripheral Blood Results Cancer Epidemiol. Biomarkers Prev., October 1, 2008; 17(10): 2835 - 2845. [Abstract] [Full Text] [PDF]

				F. Pages, J. Galon, and W. H. Fridman The essential role of the in situ immune reaction in human colorectal cancer J. Leukoc. Biol., October 1, 2008; 84(4): 981 - 987. [Abstract] [Full Text] [PDF]

				T. Schepeler, J. T. Reinert, M. S. Ostenfeld, L. L. Christensen, A. N. Silahtaroglu, L. Dyrskjot, C. Wiuf, F. J. Sorensen, M. Kruhoffer, S. Laurberg, et al. Diagnostic and Prognostic MicroRNAs in Stage II Colon Cancer Cancer Res., August 1, 2008; 68(15): 6416 - 6424. [Abstract] [Full Text] [PDF]

				Y. Jiang, G. Casey, I. C. Lavery, Y. Zhang, D. Talantov, M. Martin-McGreevy, M. Skacel, E. Manilich, A. Mazumder, D. Atkins, et al. Development of a Clinically Feasible Molecular Assay to Predict Recurrence of Stage II Colon Cancer J. Mol. Diagn., July 1, 2008; 10(4): 346 - 354. [Abstract] [Full Text] [PDF]

				I. Zlobec, L. M. Terracciano, and A. Lugli Local Recurrence in Mismatch Repair-Proficient Colon Cancer Predicted by an Infiltrative Tumor Border and Lack of CD8+ Tumor-Infiltrating Lymphocytes Clin. Cancer Res., June 15, 2008; 14(12): 3792 - 3797. [Abstract] [Full Text] [PDF]

				S. F. Shariat, J. Walz, C. G. Roehrborn, A. R. Zlotta, P. Perrotte, N. Suardi, F. Saad, and P. I. Karakiewicz External Validation of a Biomarker-Based Preoperative Nomogram Predicts Biochemical Recurrence After Radical Prostatectomy J. Clin. Oncol., March 20, 2008; 26(9): 1526 - 1531. [Abstract] [Full Text] [PDF]

				S. K. Chan, O. L. Griffith, I. T. Tai, and S. J.M. Jones Meta-analysis of Colorectal Cancer Gene Expression Profiling Studies Identifies Consistently Reported Candidate Biomarkers Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 543 - 552. [Abstract] [Full Text] [PDF]

				D. G. Nicastri, J. T. Doucette, T. E. Godfrey, and S. J. Hughes Is Occult Lymph Node Disease in Colorectal Cancer Patients Clinically Significant?: A Review of the Relevant Literature J. Mol. Diagn., November 1, 2007; 9(5): 563 - 571. [Abstract] [Full Text] [PDF]

				T. Nakamura, T. Kuwai, Y. Kitadai, T. Sasaki, D. Fan, K. R. Coombes, S.-J. Kim, and I. J. Fidler Zonal Heterogeneity for Gene Expression in Human Pancreatic Carcinoma Cancer Res., August 15, 2007; 67(16): 7597 - 7604. [Abstract] [Full Text] [PDF]

				S. Cascinu, A. Zaniboni, M. Scartozzi, and F. Meriggi Molecular Biology for Stage II Colorectal Cancer: The Jury Is Still Out J. Clin. Oncol., July 1, 2007; 25(19): 2861 - 2861. [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]

				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]

				J. Galon, W.-H. Fridman, and F. Pages The Adaptive Immunologic Microenvironment in Colorectal Cancer: A Novel Perspective Cancer Res., March 1, 2007; 67(5): 1883 - 1886. [Abstract] [Full Text] [PDF]

				Y. Hong, K. S. Ho, K. W. Eu, and P. Y. Cheah A Susceptibility Gene Set for Early Onset Colorectal Cancer That Integrates Diverse Signaling Pathways: Implication for Tumorigenesis Clin. Cancer Res., February 15, 2007; 13(4): 1107 - 1114. [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]

				M. Grade, P. Hormann, S. Becker, A. B. Hummon, D. Wangsa, S. Varma, R. Simon, T. Liersch, H. Becker, M. J. Difilippantonio, et al. Gene Expression Profiling Reveals a Massive, Aneuploidy-Dependent Transcriptional Deregulation and Distinct Differences between Lymph Node-Negative and Lymph Node-Positive Colon Carcinomas Cancer Res., January 1, 2007; 67(1): 41 - 56. [Abstract] [Full Text] [PDF]

				A. Barrier, P.-Y. Boelle, F. Roser, J. Gregg, C. Tse, D. Brault, F. Lacaine, S. Houry, M. Huguier, B. Franc, et al. Stage II Colon Cancer Prognosis Prediction by Tumor Gene Expression Profiling J. Clin. Oncol., October 10, 2006; 24(29): 4685 - 4691. [Abstract] [Full Text] [PDF]

				D. P. Harkin Genomics and the Impact of New Technologies on the Management of Colorectal Cancer Oncologist, October 1, 2006; 11(9): 988 - 991. [Abstract] [Full Text] [PDF]

				J. Yu, M. A. Mallon, W. Zhang, R. R. Freimuth, S. Marsh, M. A. Watson, P. J. Goodfellow, and H. L. McLeod DNA Repair Pathway Profiling and Microsatellite Instability in Colorectal Cancer Clin. Cancer Res., September 1, 2006; 12(17): 5104 - 5111. [Abstract] [Full Text] [PDF]

				M. Raponi, Y. Zhang, J. Yu, G. Chen, G. Lee, J. M.G. Taylor, J. MacDonald, D. Thomas, C. Moskaluk, Y. Wang, et al. Gene expression signatures for predicting prognosis of squamous cell and adenocarcinomas of the lung. Cancer Res., August 1, 2006; 66(15): 7466 - 7472. [Abstract] [Full Text] [PDF]

				S. R. Martinez, S. E. Young, R. E. Hoedema, L. J. Foshag, and A. J. Bilchik Colorectal Cancer Screening and Surveillance: Current Standards and Future Trends Ann. Surg. Oncol., June 1, 2006; 13(6): 768 - 775. [Abstract] [Full Text] [PDF]

				T. Andre, D. Sargent, J. Tabernero, M. O'Connell, M. Buyse, A. Sobrero, J.-L. Misset, C. Boni, and A. de Gramont Current Issues in Adjuvant Treatment of Stage II Colon Cancer Ann. Surg. Oncol., June 1, 2006; 13(6): 887 - 898. [Abstract] [Full Text] [PDF]

				F Al-Mulla, S AlFadhli, A H Al-Hakim, J J Going, and M S Bitar Metastatic recurrence of early-stage colorectal cancer is linked to loss of heterozygosity on chromosomes 4 and 14q. J. Clin. Pathol., June 1, 2006; 59(6): 624 - 630. [Abstract] [Full Text] [PDF]

				D. Chowdary, J. Lathrop, J. Skelton, K. Curtin, T. Briggs, Y. Zhang, J. Yu, Y. Wang, and A. Mazumder Prognostic Gene Expression Signatures Can Be Measured in Tissues Collected in RNAlater Preservative J. Mol. Diagn., February 1, 2006; 8(1): 31 - 39. [Abstract] [Full Text] [PDF]

				A. Russo, V. Bazan, B. Iacopetta, D. Kerr, T. Soussi, N. Gebbia, and for the TP53-CRC Collaborative Study Group The TP53 Colorectal Cancer International Collaborative Study on the Prognostic and Predictive Significance of p53 Mutation: Influence of Tumor Site, Type of Mutation, and Adjuvant Treatment J. Clin. Oncol., October 20, 2005; 23(30): 7518 - 7528. [Abstract] [Full Text] [PDF]

				D. Talantov, A. Mazumder, J. X. Yu, T. Briggs, Y. Jiang, J. Backus, D. Atkins, and Y. Wang Novel Genes Associated with Malignant Melanoma but not Benign Melanocytic Lesions Clin. Cancer Res., October 15, 2005; 11(20): 7234 - 7242. [Abstract] [Full Text] [PDF]

				R. A. Walgren, M. A. Meucci, and H. L. McLeod Pharmacogenomic Discovery Approaches: Will the Real Genes Please Stand Up? J. Clin. Oncol., October 10, 2005; 23(29): 7342 - 7349. [Abstract] [Full Text] [PDF]

				C. Laurent Treatment for colorectal cancer should be based on genetic analysis BMJ, October 8, 2005; 331(7520): 799 - 799. [Full Text] [PDF]

				W. L. Allen and P. G. Johnston Role of Genomic Markers in Colorectal Cancer Treatment J. Clin. Oncol., July 10, 2005; 23(20): 4545 - 4552. [Abstract] [Full Text] [PDF]

				S. Eschrich, I. Yang, G. Bloom, K. Y. Kwong, D. Boulware, A. Cantor, D. Coppola, M. Kruhoffer, L. Aaltonen, T. F. Orntoft, et al. Molecular Staging for Survival Prediction of Colorectal Cancer Patients J. Clin. Oncol., May 20, 2005; 23(15): 3526 - 3535. [Abstract] [Full Text] [PDF]

				P. G. Johnston Stage II Colorectal Cancer: To Treat or not to Treat Oncologist, May 1, 2005; 10(5): 332 - 334. [Full Text] [PDF]

				E. A. Kidd, J. Yu, X. Li, W. D. Shannon, M. A. Watson, and H. L. McLeod Variance in the Expression of 5-Fluorouracil Pathway Genes in Colorectal Cancer Clin. Cancer Res., April 1, 2005; 11(7): 2612 - 2619. [Abstract] [Full Text] [PDF]

				E. A. Poplin, J. K. Benedetti, N. C. Estes, D. G. Haller, R. J. Mayer, R. M. Goldberg, G. R. Weiss, S. E. Rivkin, and J. S. Macdonald Phase III Southwest Oncology Group 9415/Intergroup 0153 Randomized Trial of Fluorouracil, Leucovorin, and Levamisole Versus Fluorouracil Continuous Infusion and Levamisole for Adjuvant Treatment of Stage III and High-Risk Stage II Colon Cancer J. Clin. Oncol., March 20, 2005; 23(9): 1819 - 1825. [Abstract] [Full Text] [PDF]

				B. M. Ghadimi, M. Grade, M. J. Difilippantonio, S. Varma, R. Simon, C. Montagna, L. Fuzesi, C. Langer, H. Becker, T. Liersch, et al. Effectiveness of Gene Expression Profiling for Response Prediction of Rectal Adenocarcinomas to Preoperative Chemoradiotherapy J. Clin. Oncol., March 20, 2005; 23(9): 1826 - 1838. [Abstract] [Full Text] [PDF]

				F. Bertucci, P. Finetti, J. Rougemont, E. Charafe-Jauffret, V. Nasser, B. Loriod, J. Camerlo, R. Tagett, C. Tarpin, G. Houvenaeghel, et al. Gene Expression Profiling for Molecular Characterization of Inflammatory Breast Cancer and Prediction of Response to Chemotherapy Cancer Res., December 1, 2004; 64(23): 8558 - 8565. [Abstract] [Full Text] [PDF]

				A. Zaniboni and R. Labianca Adjuvant therapy for stage II colon cancer: an elephant in the living room? Ann. Onc., September 1, 2004; 15(9): 1310 - 1318. [Abstract] [Full Text] [PDF]

				P. G. Johnston Of What Value Genomics in Colorectal Cancer? Opportunities and Challenges J. Clin. Oncol., May 1, 2004; 22(9): 1538 - 1539. [Full Text] [PDF]