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

Authors
 Sang Cheul Oh ; Yun-Yong Park ; Ju-Seog Lee ; Scott Kopetz ; Timothy J Yeatman ; R Daniel Beauchamp ; J Joshua Smith ; In-Sun Chu ; Sang Cheol Kim ; Jongseung Kim ; Sang-Bae Kim ; Soo Mi Kim ; Jae Yun Lim ; Eun Sung Park 
Citation
 Gut, Vol.61(9) : 1291~1298, 2012 
Journal Title
 Gut 
ISSN
 0017-5749 
Issue Date
2012
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/90321
DOI
10.1136/gutjnl-2011-300812
Appears in Collections:
1. 연구논문 > 5. Research Institutes > Institute for Medical Convergence
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
Yonsei Authors
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