A qualitative signature for predicting pathological response to neoadjuvant chemoradiation in locally advanced rectal cancers.

Abstract

The standard therapy for locally advanced rectal cancers (LARCs) is neoadjuvant chemoradiation (nCRT) followed by surgical resection. Pathological response to nCRT varies among patients, and it remains a challenge to predict pathological response to nCRT in LARCs. Using 42 samples as the training cohort, we searched a signature by screening the gene pairs whose within-sample relative expression orderings are significantly correlated with the pathological response. The signature was validated in both a public cohort of 46 samples and a cohort of 33 samples measured at our laboratory. A signature consisting of 27 gene pairs was identified in the training cohort with an accuracy of 92.86% and an area under the receiver operating characteristic curve (AUC) of 0.95. The accuracy was 89.13% for the public test cohort and 90.91% for the private test cohort, with AUC being 0.95 and 0.91, respectively. Furthermore, the signature was used to predict disease-free survival benefits from 5Fu-based chemotherapy in 285 locally advanced colorectal cancers. The signature consisting of 27 gene pairs can robustly predict clinical response of LARCs to nCRT.