Experimentally Derived Metastasis Gene Expression Profile Predicts Recurrence and Death in Patients With Colon Cancer

J. Joshua Smith, Natasha G. Deane, Fei Wu, Nipun B. Merchant, Bing Zhang, Aixiang Jiang, Pengcheng Lu, J. Chad Johnson, Carl Schmidt, Christina E. Bailey, Steven Eschrich, Christian Kis, Shawn Levy, M. Kay Washington, Martin J. Heslin, Robert J. Coffey, Timothy J. Yeatman, Yu Shyr, R. Daniel Beauchamp

Research output: Contribution to journalArticle

339 Scopus citations

Abstract

Background & Aims: Staging inadequately predicts metastatic risk in patients with colon cancer. We used a gene expression profile derived from invasive, murine colon cancer cells that were highly metastatic in an immunocompetent mouse model to identify patients with colon cancer at risk of recurrence. Methods: This phase 1, exploratory biomarker study used 55 patients with colorectal cancer from Vanderbilt Medical Center (VMC) as the training dataset and 177 patients from the Moffitt Cancer Center as the independent dataset. The metastasis-associated gene expression profile developed from the mouse model was refined with comparative functional genomics in the VMC gene expression profiles to identify a 34-gene classifier associated with high risk of metastasis and death from colon cancer. A recurrence score derived from the biologically based classifier was tested in the Moffitt dataset. Results: A high score was significantly associated with increased risk of metastasis and death from colon cancer across all pathologic stages and specifically in stage II and stage III patients. The recurrence score was shown to independently predict risk of cancer recurrence and death in univariate and multivariate models. For example, among stage III patients, a high score translated to increased relative risk of cancer recurrence (hazard ratio, 4.7; 95% confidence interval, 1.566-14.05). Furthermore, the recurrence score identified patients with stage III disease whose 5-year recurrence-free survival was >88% and for whom adjuvant chemotherapy did not increase survival time. Conclusion: A gene expression profile identified from an experimental model of colon cancer metastasis predicted cancer recurrence and death, independently of conventional measures, in patients with colon cancer.

Original languageEnglish (US)
Pages (from-to)958-968
Number of pages11
JournalGastroenterology
Volume138
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Keywords

  • Colon Cancer Prognosis
  • Gene Expression Profiling
  • Mouse Model
  • Predictive Gene Signature

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Smith, J. J., Deane, N. G., Wu, F., Merchant, N. B., Zhang, B., Jiang, A., Lu, P., Johnson, J. C., Schmidt, C., Bailey, C. E., Eschrich, S., Kis, C., Levy, S., Washington, M. K., Heslin, M. J., Coffey, R. J., Yeatman, T. J., Shyr, Y., & Beauchamp, R. D. (2010). Experimentally Derived Metastasis Gene Expression Profile Predicts Recurrence and Death in Patients With Colon Cancer. Gastroenterology, 138(3), 958-968. https://doi.org/10.1053/j.gastro.2009.11.005