The current study suggests that the identification of predictive signatures of fluorouracil (5-FU) response for stage II and III colorectal cancer (CRC) could be confounded by chemotherapy-irrelevant low relapse risk. Using the samples of patients with stage II and III CRC who were treated with curative surgery only, we identified a signature with which to predict chemotherapy-irrelevant relapse risk for patients after curative surgery. By applying this signature to the samples of patients with stage II and III CRC who were treated with 5-FU-based adjuvant chemotherapy (ACT) after surgery, we predicted the relapse risk if treated with surgery only. From high-risk samples, we further identified another signature with which to predict therapeutic benefit from 5-FU-based ACT. On the basis of the relative expression orderings of gene pairs, a postsurgery relapse risk signature that consisted of 44 gene pairs was developed and verified in 3 independent data sets. A 5-FU therapeutic benefit signature that consisted of 4 gene pairs was then developed to predict the response of 5-FU-based ACT for those patients with high relapse risk after curative surgery. The signature was verified in 4 independent datasets. For patients with stage II and III CRC, the coupled signatures can first identify patients with high relapse risk after curative surgery, then predict therapeutic benefit from 5-FU-based ACT.-Song, K., Guo, Y., Wang, X., Cai, H., Zheng, W., Li, N., Song, X., Ao, L., Guo, Z., Zhao, W. Transcriptional signatures for coupled predictions of stage II and III colorectal cancer metastasis and fluorouracil-based adjuvant chemotherapy benefit.
Keywords: CRC; fluorouracil; relapse risk; relative expression orderings.