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Prognostic gene expression signature associated with two molecularly distinct subtypes of colorectal cancer.

 Sang Cheul Oh  ;  Yun-Yong Park  ;  Eun Sung Park  ;  Jae Yun Lim  ;  Soo Mi Kim  ;  Sang-Bae Kim  ;  Jongseung Kim  ;  Sang Cheol Kim  ;  In-Sun Chu  ;  J Joshua Smith  ;  R Daniel Beauchamp  ;  Timothy J Yeatman  ;  Scott Kopetz  ;  Ju-Seog Lee 
 Gut, Vol.61(9) : 1291-1298, 2012 
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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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Medical Convergence (연의-생공연 메디컬융합연구소) > 1. Journal Papers
Yonsei Authors
Park, Eun Sung(박은성)
Lim, Jae Yun(임재윤)
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