Chen Hengyu, Ma Xianxiong, Yang Ming, Wang Mengyi, Li Lei, Huang Tao
Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
NHC Key Laboratory of Hormones and Development, Tianjin Institute of Endocrinology, Tianjin Medical University Chu Hsien-I Memorial Hospital, Tianjin, China.
Front Genet. 2020 Apr 24;11:333. doi: 10.3389/fgene.2020.00333. eCollection 2020.
Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer-related death in young women. Several prognostic and predictive transcription factor (TF) markers have been reported for BC; however, they are inconsistent due to small datasets, the heterogeneity of BC, and variation in data pre-processing approaches. This study aimed to identify an effective predictive TF signature for the prognosis of patients with BC. We analyzed the TF data of 868 patients with BC in The Cancer Genome Atlas (TCGA) database to investigate TF biomarkers relevant to recurrence-free survival (RFS). These patients were separated into training and internal validation datasets, with GSE2034 and GSE42568 used as external validation sets. A nine-TF signature was identified as crucially related to the RFS of patients with BC by univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and multivariate Cox proportional hazard analysis in the training dataset. Kaplan-Meier analysis revealed that the nine-TF signature could significantly distinguish high- and low-risk patients in both the internal validation dataset and the two external validation sets. Receiver operating characteristic (ROC) analysis further verified that the nine-TF signature showed a good performance for predicting the RFS of patients with BC. In addition, we developed a nomogram based on risk score and lymph node status, with C-index, ROC, and calibration plot analysis, suggesting that it displays good performance and clinical value. In summary, we used integrated bioinformatics approaches to identify an effective predictive nine-TF signature which may be a potential biomarker for BC prognosis.
乳腺癌(BC)是年轻女性中最常被诊断出的癌症,也是癌症相关死亡的主要原因。已有多项用于乳腺癌的预后和预测转录因子(TF)标志物被报道;然而,由于数据集较小、乳腺癌的异质性以及数据预处理方法的差异,这些标志物并不一致。本研究旨在识别一种有效的预测性TF特征,用于乳腺癌患者的预后评估。我们分析了癌症基因组图谱(TCGA)数据库中868例乳腺癌患者的TF数据,以研究与无复发生存期(RFS)相关的TF生物标志物。这些患者被分为训练集和内部验证集,GSE2034和GSE42568用作外部验证集。通过单变量Cox比例风险分析、最小绝对收缩和选择算子(LASSO)Cox回归分析以及训练数据集中的多变量Cox比例风险分析,确定了一个与乳腺癌患者RFS密切相关的九TF特征。Kaplan-Meier分析表明,该九TF特征在内部验证集和两个外部验证集中均能显著区分高风险和低风险患者。受试者工作特征(ROC)分析进一步证实,该九TF特征在预测乳腺癌患者RFS方面表现良好。此外,我们基于风险评分和淋巴结状态开发了一种列线图,通过C指数、ROC和校准曲线分析表明,它具有良好的性能和临床价值。总之,我们使用综合生物信息学方法识别了一种有效的预测性九TF特征,它可能是乳腺癌预后的潜在生物标志物。