Identification of a 14-gene signature that predicts survival in colorectal cancer with liver metastasis.

Abstract

e14037 Background: Colorectal cancer (CRC) is the third leading cause of cancer death in men and women combined in the USA. Colorectal liver metastasis (CLM), the most common metastasis of CRC, accounts for at least two thirds of CRC deaths. The purpose of this study is to identify a gene signature that predicts patient survival in patients with CLM. Methods: We analyzed the gene expression profiles of specimens from 24 CLM patients (M:F = 14:10) who underwent metastatic liver resection and unmatched primary CRC specimens from an independent cohort of 30 patients (M:F = 14:16). The association between gene expression levels and survival outcome was evaluated using Cox proportional hazards regression. Random Forests and risk scores were used to construct a gene expression-based survival classifier. Results: Based on survival classifier of CLM patients, a 14-gene signature was developed. According to leave-one-out cross validation, all 24 CLM patients (median follow-up time of 25 months) were correctly assigned into high-risk or low-risk groups (p=0.001). This 14-gene signature was then validated in an independent cohort of 30 primary CRC patients (median follow-up time of 42.2 months; p= 0.03) and a subset of 11 patients who were diagnosed at presentation or follow-up with liver metastasis (M:F = 5:6; median follow-up time of 27.6 months; p=0.04). Conclusions: We have identified a 14-gene signature that predicts the survival of CLM patients after liver resection, with validation in an independent cohort. Although sample size is small, the significance level achieved with our survival analysis warrants further investigation of this 14-gene signature in a larger sample size.