Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapy

Abstract 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 neoadj...

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Main Authors: Ziping Wu, Lei Zhang, Shuguang Xu, Yanping Lin, Wenjin Yin, Jinglu Lu, Rui Sha, Xiaonan Sheng, Liheng Zhou, Jinsong Lu
Format: Article
Language:English
Published: BMC 2019-03-01
Series:Cancer Cell International
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12935-019-0793-2
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author Ziping Wu
Lei Zhang
Shuguang Xu
Yanping Lin
Wenjin Yin
Jinglu Lu
Rui Sha
Xiaonan Sheng
Liheng Zhou
Jinsong Lu
author_facet Ziping Wu
Lei Zhang
Shuguang Xu
Yanping Lin
Wenjin Yin
Jinglu Lu
Rui Sha
Xiaonan Sheng
Liheng Zhou
Jinsong Lu
author_sort Ziping Wu
collection DOAJ
description Abstract 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, p = 0.023) and multivariate (OR = 0.074, 95% CI 0.011–0.475, p = 0.006) logistic regression analyses. High ZEB1 protein expression was also associated with a short DFS according to both the log-rank test (p = 0.023) and Cox proportional hazard model (HR = 9.025, 95% CI 1.024–79.519, p = 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, p = 0.005) and a poorer DFS (HR = 10.516, 95% CI 1.171–94.435, p = 0.036) compared with low ZEB1 protein expression. In HER2-overexpressing patients, ZEB1 protein expression was also associated with poor survival (p = 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. Trial registration 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
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spelling doaj.art-64987442433549e2871d4688c4dcf04c2022-12-22T00:42:00ZengBMCCancer Cell International1475-28672019-03-011911910.1186/s12935-019-0793-2Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapyZiping Wu0Lei Zhang1Shuguang Xu2Yanping Lin3Wenjin Yin4Jinglu Lu5Rui Sha6Xiaonan Sheng7Liheng Zhou8Jinsong Lu9Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract 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, p = 0.023) and multivariate (OR = 0.074, 95% CI 0.011–0.475, p = 0.006) logistic regression analyses. High ZEB1 protein expression was also associated with a short DFS according to both the log-rank test (p = 0.023) and Cox proportional hazard model (HR = 9.025, 95% CI 1.024–79.519, p = 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, p = 0.005) and a poorer DFS (HR = 10.516, 95% CI 1.171–94.435, p = 0.036) compared with low ZEB1 protein expression. In HER2-overexpressing patients, ZEB1 protein expression was also associated with poor survival (p = 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. Trial registration 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=1http://link.springer.com/article/10.1186/s12935-019-0793-2Breast cancerNeoadjuvant chemotherapyZEB1PredictivePrognostic
spellingShingle Ziping Wu
Lei Zhang
Shuguang Xu
Yanping Lin
Wenjin Yin
Jinglu Lu
Rui Sha
Xiaonan Sheng
Liheng Zhou
Jinsong Lu
Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapy
Cancer Cell International
Breast cancer
Neoadjuvant chemotherapy
ZEB1
Predictive
Prognostic
title Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapy
title_full Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapy
title_fullStr Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapy
title_full_unstemmed Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapy
title_short Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapy
title_sort predictive and prognostic value of zeb1 protein expression in breast cancer patients with neoadjuvant chemotherapy
topic Breast cancer
Neoadjuvant chemotherapy
ZEB1
Predictive
Prognostic
url http://link.springer.com/article/10.1186/s12935-019-0793-2
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