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Prognostic gene expression signature associated with two molecularly distinct subtypes of colorectal cancer
  1. Sang Cheul Oh1,2,
  2. Yun-Yong Park1,
  3. Eun Sung Park1,3,
  4. Jae Yun Lim1,4,
  5. Soo Mi Kim5,
  6. Sang-Bae Kim1,
  7. Jongseung Kim1,
  8. Sang Cheol Kim6,
  9. In-Sun Chu6,
  10. J Joshua Smith7,8,
  11. R Daniel Beauchamp7,8,
  12. Timothy J Yeatman9,
  13. Scott Kopetz10,
  14. Ju-Seog Lee1
  1. 1Department of Systems Biology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  2. 2Division of Hemato-Oncology, Department of Internal Medicine, Korea University Medical Center, Korea University College of Medicine, Seoul, Korea
  3. 3Institute for Medical Convergence, Yonsei University College of Medicine, Seoul, Korea
  4. 4Department of Medical Oncology, Yonsei University College of Medicine, Seoul, Korea
  5. 5Department of Physiology, Chonbuk National University Medical School and Hospital, Jeonju, Korea
  6. 6Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
  7. 7Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  8. 8Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
  9. 9Department of Surgery, Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
  10. 10Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  1. Correspondence to Dr Ju-Seog Lee, Department of Systems Biology, Division of Cancer Medicine, Unit 950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA; jlee{at}mdanderson.org

Abstract

Aims Despite continual efforts to develop prognostic and predictive models of colorectal cancer by using clinicopathological and genetic parameters, a clinical test that can discriminate between patients with good or poor outcome after treatment has not been established. Thus, the authors aim to uncover subtypes of colorectal cancer that have distinct biological characteristics associated with prognosis and identify potential biomarkers that best reflect the biological and clinical characteristics of subtypes.

Methods Unsupervised hierarchical clustering analysis was applied to gene expression data from 177 patients with colorectal cancer to determine a prognostic gene expression signature. Validation of the signature was sought in two independent patient groups. The association between the signature and prognosis of patients was assessed by Kaplan–Meier plots, log-rank tests and the Cox model.

Results The authors identified a gene signature that was associated with overall survival and disease-free survival in 177 patients and validated in two independent cohorts of 213 patients. In multivariate analysis, the signature was an independent risk factor (HR 3.08; 95% CI 1.33 to 7.14; p=0.008 for overall survival). Subset analysis of patients with AJCC (American Joint Committee on Cancer) stage III cancer revealed that the signature can also identify the patients who have better outcome with adjuvant chemotherapy (CTX). Adjuvant chemotherapy significantly affected disease-free survival in patients in subtype B (3-year rate, 71.2% (CTX) vs 41.9% (no CTX); p=0.004). However, such benefit of adjuvant chemotherapy was not significant for patients in subtype A.

Conclusion The gene signature is an independent predictor of response to chemotherapy and clinical outcome in patients with colorectal cancer.

  • Colorectal cancer
  • microarrays
  • gene expression profile
  • prognostic marker
  • predictive markers
  • chemotherapy
  • colorectal carcinoma
  • liver metabolism
  • gastric cancer
  • cancer
  • cancer genetics
  • liver
  • hepatoma

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Footnotes

  • SC Oh and Y-Y Park contributed equally to this study.

  • Funding This study was supported by the G. S. Hogan Gastrointestinal Research Fund from The University of Texas MD Anderson Cancer Center, and partially by CA069457, CA095103, CA068485, and GM088822.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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