ZEB1蛋白表达在接受新辅助化疗的乳腺癌患者中的预测和预后价值
Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapy.
作者信息
Wu Ziping, Zhang Lei, Xu Shuguang, Lin Yanping, Yin Wenjin, Lu Jinglu, Sha Rui, Sheng Xiaonan, Zhou Liheng, Lu Jinsong
机构信息
Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, No. 160 Pujian Road, Pudong New District, Shanghai, 200127 People's Republic of China.
出版信息
Cancer Cell Int. 2019 Mar 29;19:78. doi: 10.1186/s12935-019-0793-2. eCollection 2019.
BACKGROUND
Zinc finger E-box binding homeobox 1 (ZEB1) is a molecule involved in the progression of epithelial-to-mesenchymal transition (EMT) in various kinds of cancers. Here, we aimed to determine whether the expression of the ZEB1 protein is related to the response of patients to neoadjuvant therapy as well as their survival outcome.
METHODS
Immunohistochemistry (IHC) was performed on paraffin-embedded tumor samples from core needle biopsy before neoadjuvant therapy (NAT). Univariate and multivariate logistic regression analyses were used to analyze the associations between the protein expression of ZEB1 and the pathological complete response (pCR) outcome. Kaplan-Meier plots and log-rank tests were used to compare disease-free survival (DFS) between groups. A Cox proportional hazards model was used to calculate the adjusted hazard ratio (HR) with a 95% confidential interval (95% CI).
RESULTS
A total of 75 patients were included in the IHC test. High ZEB1 protein expression was associated with a low pCR rate in both univariate (OR = 0.260, 95% CI 0.082-0.829, = 0.023) and multivariate (OR = 0.074, 95% CI 0.011-0.475, = 0.006) logistic regression analyses. High ZEB1 protein expression was also associated with a short DFS according to both the log-rank test (= 0.023) and Cox proportional hazard model (HR = 9.025, 95% CI 1.024-79.519, = 0.048). In hormone receptor positive (HorR-positive) patients, high ZEB1 protein expression was also associated with a lower pCR (OR = 0.054, 95% CI 0.007-0.422, = 0.005) and a poorer DFS (HR = 10.516, 95% CI 1.171-94.435, = 0.036) compared with low ZEB1 protein expression. In HER2-overexpressing patients, ZEB1 protein expression was also associated with poor survival (= 0.042).
CONCLUSIONS
Our results showed that high ZEB1 protein expression was a negative predictive marker of pCR and DFS in neoadjuvant therapy in breast cancer patients and in HorR-positive and HER2-overexpressing subgroups. NCT, NCT02199418. Registered 24 July 2014-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02199418?term=NCT02199418&rank=1. NCT, NCT 02221999. Registered 21 August 2014-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02221999?term=NCT02221999&rank=1.
背景
锌指E盒结合同源框蛋白1（ZEB1）是一种参与多种癌症上皮-间质转化（EMT）进程的分子。在此，我们旨在确定ZEB1蛋白的表达是否与患者对新辅助治疗的反应及其生存结果相关。
方法
对新辅助治疗（NAT）前粗针穿刺活检获得的石蜡包埋肿瘤样本进行免疫组织化学（IHC）检测。采用单因素和多因素逻辑回归分析来分析ZEB1蛋白表达与病理完全缓解（pCR）结果之间的关联。使用Kaplan-Meier曲线和对数秩检验来比较各组之间的无病生存期（DFS）。采用Cox比例风险模型计算调整后的风险比（HR）及95%置信区间（95%CI）。
结果
共有75例患者纳入IHC检测。在单因素（OR = 0.260，95%CI 0.082 - 0.829，P = 0.023）和多因素（OR = 0.074，95%CI 0.011 - 0.475，P = 0.006）逻辑回归分析中，ZEB1蛋白高表达均与低pCR率相关。根据对数秩检验（P = 0.023）和Cox比例风险模型（HR = 9.025，95%CI 1.024 - 79.519，P = 0.048），ZEB1蛋白高表达也与较短的DFS相关。在激素受体阳性（HorR阳性）患者中，与ZEB1蛋白低表达相比，ZEB1蛋白高表达也与较低的pCR（OR = 0.054，95%CI 0.007 - 0.422，P = 0.005）和较差的DFS（HR = 10.516，95%CI 1.171 - 94.435，P = 0.036）相关。在HER2过表达患者中，ZEB1蛋白表达也与不良生存相关（P = 0.042）。
结论
我们的结果表明，ZEB1蛋白高表达是乳腺癌患者新辅助治疗中pCR和DFS的阴性预测标志物，在HorR阳性和HER2过表达亚组中也是如此。NCT，NCT02199418。于2014年7月24日注册——回顾性注册，https://clinicaltrials.gov/ct2/show/NCT02199418?term=NCT02199418&rank=1。NCT，NCT 02221999。于2014年8月21日注册——回顾性注册，https://clinicaltrials.gov/ct2/show/NCT02221999?term=NCT02221999&rank=1。
Zotero 插件