title: Prognostic gene expression signature associated with two molecularly distinct subtypes of colorectal cancer.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The gene signature is an independent predictor of response to chemotherapy and clinical outcome in patients with colorectal cancer.
authors: Department of Systems Biology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors: Sang Cheul
authors: SC
authors: Oh
authors: Yun-Yong
authors: YY
authors: Park
authors: Eun Sung
authors: ES
authors: Park
authors: Jae Yun
authors: JY
authors: Lim
authors: Soo Mi
authors: SM
authors: Kim
authors: Sang-Bae
authors: SB
authors: Kim
authors: Jongseung
authors: J
authors: Kim
authors: Sang Cheol
authors: SC
authors: Kim
authors: In-Sun
authors: IS
authors: Chu
authors: J Joshua
authors: JJ
authors: Smith
authors: R Daniel
authors: RD
authors: Beauchamp
authors: Timothy J
authors: TJ
authors: Yeatman
authors: Scott
authors: S
authors: Kopetz
authors: Ju-Seog
authors: JS
authors: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D016000:Cluster Analysis; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents