Transcriptional signatures for coupled predictions of stage II and III colorectal cancer metastasis and fluorouracil‐based adjuvant chemotherapy benefit

ABSTRACT 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. FASEB J. 33, 151–162 (2019). www.fasebj.org