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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BMC
2019-03-01
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Series: | Cancer Cell International |
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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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issn | 1475-2867 |
language | English |
last_indexed | 2024-12-12T02:07:20Z |
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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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