Data_Sheet_6_A 41-Gene Pair Signature for Predicting the Pathological Response of Locally Advanced Rectal Cancer to Neoadjuvant Chemoradiation.XLSX

Background and Purpose: Pathological response status is a standard reference for the early evaluation of the effect of neoadjuvant chemoradiation (nCRT) on locally advanced rectal cancer (LARC) patients. Various patients respond differently to nCRT, but identifying the pathological response of LARC to nCRT remains a challenge. Therefore, we aimed to identify a signature that can predict the response of LARC to nCRT.Material and Methods: The gene expression profiles of 111 LARC patients receiving fluorouracil-based nCRT were used to obtain gene pairs with within-sample relative expression orderings related to pathological response. These reversal gene pairs were ranked according to the mean decrease Gini index provided by the random forest algorithm to obtain the signature. This signature was verified in two public cohorts of 46 and 42 samples, and a cohort of 33 samples measured at our laboratory. In addition, the signature was used to predict disease-free survival benefits in a series of colorectal cancer datasets.Results: A 41-gene pair signature (41-GPS) was identified in the training cohort with an accuracy of 84.68% and an area under the receiver operating characteristic curve (AUC) of 0.94. In the two public test cohorts, the accuracy was 93.37 and 73.81%, with AUCs of 0.97 and 0.86, respectively. In our dataset, the AUC was 0.80. The results of the survival analysis show that 41-GPS plays an effective role in identifying patients who will respond to nCRT and have a better prognosis.Conclusion: The signature consisting of 41 gene pairs can robustly predict the clinical pathological response of LARC patients to nCRT.

背景与目的：病理反应状态是评估新辅助放化疗（nCRT）对局部晚期直肠癌（LARC）患者早期疗效的标准参照。患者对新辅助放化疗的反应各异，但识别LARC对nCRT的病理反应仍是一大挑战。因此，本研究旨在鉴定一种能够预测LARC对nCRT反应的标志。材料与方法：利用111例接受基于氟尿嘧啶的新辅助放化疗的LARC患者的基因表达谱，获取与病理反应相关的样本内基因对相对表达顺序。根据随机森林算法提供的平均减少基尼指数对这些反转基因对进行排序，以获得标志。该标志在两个包含46和42个样本的公共队列以及我们实验室测量的33个样本队列中得到验证。此外，该标志还用于预测一系列结直肠癌数据集中的无病生存期益处。结果：在训练队列中鉴定出41个基因对标志（41-GPS），其准确率为84.68%，接受者操作特征曲线（AUC）下面积为0.94。在两个公共测试队列中，准确率分别为93.37%和73.81%，AUC分别为0.97和0.86。在我们的数据集中，AUC为0.80。生存分析结果表明，41-GPS在识别对nCRT有反应且预后较好的患者方面发挥着有效的作用。结论：由41个基因对组成的标志能够稳健地预测LARC患者对nCRT的临床病理反应。