Shigemizu Daichi, Iwase Takuji, Yoshimoto Masataka, Suzuki Yasuyo, Miya Fuyuki, Boroevich Keith A, Katagiri Toyomasa, Zembutsu Hitoshi, Tsunoda Tatsuhiko
Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Laboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Cancer Med. 2017 Jul;6(7):1627-1638. doi: 10.1002/cam4.1092. Epub 2017 May 24.
The goal of this study is to establish a method for predicting overall survival (OS) and disease-free survival (DFS) in breast cancer patients after surgical operation. The gene expression profiles of cancer tissues from the patients, who underwent complete surgical resection of breast cancer and were subsequently monitored for postoperative survival, were analyzed using cDNA microarrays. We detected seven and three probes/genes associated with the postoperative OS and DFS, respectively, from our discovery cohort data. By incorporating these genes associated with the postoperative survival into MammaPrint genes, often used to predict prognosis of patients with early-stage breast cancer, we constructed postoperative OS and DFS prediction models from the discovery cohort data using a Cox proportional hazard model. The predictive ability of the models was evaluated in another independent cohort using Kaplan-Meier (KM) curves and the area under the receiver operating characteristic curve (AUC). The KM curves showed a statistically significant difference between the predicted high- and low-risk groups in both OS (log-rank trend test P = 0.0033) and DFS (log-rank trend test P = 0.00030). The models also achieved high AUC scores of 0.71 in OS and of 0.60 in DFS. Furthermore, our models had improved KM curves when compared to the models using MammaPrint genes (OS: P = 0.0058, DFS: P = 0.00054). Similar results were observed when our model was tested in publicly available datasets. These observations indicate that there is still room for improvement in the current methods of predicting postoperative OS and DFS in breast cancer.
本研究的目的是建立一种预测乳腺癌患者手术后总生存期(OS)和无病生存期(DFS)的方法。使用cDNA微阵列分析了接受乳腺癌完整手术切除并随后进行术后生存监测的患者癌组织的基因表达谱。我们从发现队列数据中分别检测到与术后OS和DFS相关的7个和3个探针/基因。通过将这些与术后生存相关的基因纳入常用于预测早期乳腺癌患者预后的MammaPrint基因中,我们使用Cox比例风险模型从发现队列数据构建了术后OS和DFS预测模型。使用Kaplan-Meier(KM)曲线和受试者工作特征曲线下面积(AUC)在另一个独立队列中评估模型的预测能力。KM曲线显示,预测的高风险组和低风险组在OS(对数秩趋势检验P = 0.0033)和DFS(对数秩趋势检验P = 0.00030)方面均存在统计学显著差异。模型在OS中的AUC得分也达到了0.71,在DFS中达到了0.60。此外,与使用MammaPrint基因的模型相比,我们的模型具有更好的KM曲线(OS:P = 0.0058,DFS:P = 0.00054)。在公开可用的数据集中测试我们的模型时也观察到了类似的结果。这些观察结果表明,目前预测乳腺癌术后OS和DFS的方法仍有改进空间。