ColoFinder: a prognostic 9-gene signature improves prognosis for 871 stage II and III colorectal cancer patients.

Mingguang Shi,Jianmin He

doi:10.7717/peerj.1804

Abstract

Colorectal cancer (CRC) is a heterogeneous disease with a high mortality rate and is still lacking an effective treatment. Our goal is to develop a robust prognosis model for predicting the prognosis in CRC patients. In this study, 871 stage II and III CRC samples were collected from six gene expression profilings. ColoFinder was developed using a 9-gene signature based Random Survival Forest (RSF) prognosis model. The 9-gene signature recurrence score was derived with a 5-fold cross validation to test the association with relapse-free survival, and the value of AUC was gained with 0.87 in GSE39582(95% CI [0.83–0.91]). The low-risk group had a significantly better relapse-free survival (HR, 14.8; 95% CI [8.17–26.8]; P < 0.001) than the high-risk group. We also found that the 9-gene signature recurrence score contributed more information about recurrence than standard clinical and pathological variables in univariate and multivariate Cox analyses when applied to GSE17536(p = 0.03 and p = 0.01 respectively). Furthermore, ColoFinder improved the predictive ability and better stratified the risk subgroups when applied to CRC gene expression datasets GSE14333, GSE17537, GSE12945and GSE24551. In summary, ColoFinder significantly improves the risk assessment in stage II and III CRC patients. The 9-gene prognostic classifier informs patient prognosis and treatment response.

Highlights

According to the American Joint Committee on Cancer (AJCC) stage of colorectal cancer (CRC), 5-year survival rates are 82.5% for stage II and 59.5% for stage III CRC patients respectively (O’Connell, Maggard & Ko, 2004)
The results demonstrated that ColoFinder improved the predicted performance of prognosis and provided the concise testing result for general application in clinical trials
A major conclusion from this study was that ColoFinder was able to predict the prognosis for stage II and III CRC patients

Summary

Introduction

According to the American Joint Committee on Cancer (AJCC) stage of colorectal cancer (CRC), 5-year survival rates are 82.5% for stage II and 59.5% for stage III CRC patients respectively (O’Connell, Maggard & Ko, 2004). 5-year stagespecific survivals are 72.2% for stage IIB (T-stage 4, lymph node–negative) and 83.4% for stage IIIA (T-stage 1–2, lymph node–positive) CRC patients. Stage IIB is significantly poorer survival than stage IIIA (O’Connell, Maggard & Ko, 2004). There are approximately 20% of stage II CRC patients who do not make the expected benefits from the adjuvant chemotherapy (CTX). 42–44% of stage III patients treated by surgery alone do not recur in 5 years (Ragnhammar et al, 2001). Based on these observations, it underlines the need for accurate assessment of recurrent risk for stage II

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