RT Journal Article SR Electronic T1 Prognostic gene expression signature associated with two molecularly distinct subtypes of colorectal cancer JF Gut JO Gut FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1291 OP 1298 DO 10.1136/gutjnl-2011-300812 VO 61 IS 9 A1 Sang Cheul Oh A1 Yun-Yong Park A1 Eun Sung Park A1 Jae Yun Lim A1 Soo Mi Kim A1 Sang-Bae Kim A1 Jongseung Kim A1 Sang Cheol Kim A1 In-Sun Chu A1 J Joshua Smith A1 R Daniel Beauchamp A1 Timothy J Yeatman A1 Scott Kopetz A1 Ju-Seog Lee YR 2012 UL http://gut.bmj.com/content/61/9/1291.abstract AB 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.