Comparison of Prognostic Genomic Predictors in Colorectal Cancer

Yun-Yong Park,Ju-Seog Lee,Sang Bae Kim,Sung Soo Kim,Woojin Jeong,Sang Cheul Oh,Scott Kopetz,In-Sun Chu,Sang Cheol Kim,Bo Hwa Sohn,Jae Yun Lim,Sung Sook Lee,Eun Sung Park,Patrick Tan

doi:10.1371/journal.pone.0060778

Abstract

BackgroundAlthough several prognostic genomic predictors have been identified from independent studies, it remains unclear whether these predictors are actually concordant with respect to their predictions for individual patients and which predictor performs best. We compared five prognostic genomic predictors, the V7RHS, the ColoGuideEx, the Meta163, the OncoDX, and the MDA114, in terms of predicting disease-free survival in two independent cohorts of patients with colorectal cancer.Study DesignUsing original classification algorithms, we tested the predictions of five genomic predictors for disease-free survival in two cohorts of patients with colorectal cancer (n = 229 and n = 168) and evaluated concordance of predictors in predicting outcomes for individual patients.ResultsWe found that only two predictors, OncoDX and MDA114, demonstrated robust performance in identifying patients with poor prognosis in 2 independent cohorts. These two predictors also had modest but significant concordance of predicted outcome (r>0.3, P<0.001 in both cohorts).ConclusionsFurther validation of developed genomic predictors is necessary. Despite the limited number of genes shared by OncoDX and MDA114, individual-patient outcomes predicted by these two predictors were significantly concordant.

Highlights

Colorectal cancer is the second-leading cause of death from cancer in the United States, and about 40% of new cases are diagnosed while the cancer is in the early or localized stage [1]
Clinicopathological staging systems such as the Dukes system and the American Joint Committee on Cancer (AJCC) system have been the gold standards as prognostic indicators [2,3,4], developing improved prognostic tools is important because the clinical predictors used currently provide only broad categorization of risk and fail to identify biological characteristics important for matching patients with specific therapies
The 5 prognostic genomic predictors we examined were the (i) Veridex 7-gene relapse hazard score (V7RHS) developed by Jiang et al [7], (ii) metastasis-associated 163-gene expression signature (Meta163) developed by Jorissen et al [5], (iii) 7-gene Oncotype

Summary

Introduction

Colorectal cancer is the second-leading cause of death from cancer in the United States, and about 40% of new cases are diagnosed while the cancer is in the early or localized stage [1]. Clinicopathological staging systems such as the Dukes system and the American Joint Committee on Cancer (AJCC) system have been the gold standards as prognostic indicators [2,3,4], developing improved prognostic tools is important because the clinical predictors used currently provide only broad categorization of risk and fail to identify biological characteristics important for matching patients with specific therapies. A similar genomic prognostic predictor was developed at The University of Texas MD Anderson Cancer Center [6]. We compared five prognostic genomic predictors, the V7RHS, the ColoGuideEx, the Meta163, the OncoDX, and the MDA114, in terms of predicting disease-free survival in two independent cohorts of patients with colorectal cancer

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Conclusion