ColoGuidePro: A prognostic 7-gene expression signature for stage III colorectal cancer patients
By: Sveen A, Agesen TH, Nesbakken A, Meling GI, Rognum TO, Liestol K, Skotheim RI, Lothe RA.

Department of Cancer Prevention, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital.
Clin Cancer Res. 2012 Sep 18.

Abstract

Purpose

Improved prognostic stratification of stage II and III colorectal cancer patients is warranted for post-operative clinical decision making. This study was conducted to develop a clinically feasible and robust prognostic classifier for these patients independent of adjuvant treatment.

Experimental Design

Global gene expression profiles from altogether 387 stage II and III colorectal cancer tissue samples from three independent patient series were included in the study. ColoGuidePro, a 7-gene prognostic classifier, was developed from a selected Norwegian learning series (n = 95; no adjuvant treatment) using lasso-penalized multivariate survival modeling with cross-validation.

Results

The expression signature significantly stratified patients in a consecutive Norwegian test series, where patients were treated according to current standards (hazard ratio = 2.9 [1.1, 7.5]; P = 0.03; n = 77), and an external validation series (hazard ratio = 3.7 [2.0, 6.8]; P < 0.001; n = 215) according to survival. ColoGuidePro was also an independent predictor of prognosis in multivariate models including tumor stage in both series (hazard ratio ≥ 3.1; P ≤ 0.03). In the validation series, which consisted of patients from other populations (USA and Australia), 5-year relapse-free survival was significantly predicted for stage III patients only (P < 0.001; n = 107). Here, prognostic stratification was independent of adjuvant treatment (P = 0.001).

Conclusions

We present ColoGuidePro, a prognostic classifier developed for stage II and III colorectal cancer patients. The test is suitable for transfer to clinical use, and has best prognostic prediction potential for stage III patients.

PMID: 22991413 [PubMed - as supplied by publisher] Source: National Library of Medicine.







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