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Cancer Cell International
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Breast Cancer | Primary research

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

Authors: Ziping Wu, Lei Zhang, Shuguang Xu, Yanping Lin, Wenjin Yin, Jinglu Lu, Rui Sha, Xiaonan Sheng, Liheng Zhou, Jinsong Lu

Published in: Cancer Cell International | Issue 1/2019

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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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Metadata
Title
Predictive and prognostic value of ZEB1 protein expression in breast cancer patients with neoadjuvant chemotherapy
Authors
Ziping Wu
Lei Zhang
Shuguang Xu
Yanping Lin
Wenjin Yin
Jinglu Lu
Rui Sha
Xiaonan Sheng
Liheng Zhou
Jinsong Lu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0793-2

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