Excessive glutathione intake contributes to chemotherapy resistance in breast cancer: a propensity score matching analysis

Abstract Background We aim to explore the impact of excessive glutathione (GSH) intake on chemotherapy sensitivity in breast cancer. Methods Clinicopathological data were collected from 460 breast cancer patients who underwent adjuvant chemotherapy from January 2016 to December 2019 from Zhengzhou U...

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Main Authors: Zhiyuan Zhang, Jiaru Gao, Linjiao Jia, Shuxin Kong, Maosen Zhai, Shuai Wang, Wenwen Li, Shoukai Wang, Yuqing Su, Wanyue Li, Changzheng Zhu, Wenkang Wang, Yuanxiang Lu, Wentao Li
Format: Article
Language:English
Published: BMC 2024-12-01
Series:World Journal of Surgical Oncology
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Online Access:https://doi.org/10.1186/s12957-024-03626-9
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author Zhiyuan Zhang
Jiaru Gao
Linjiao Jia
Shuxin Kong
Maosen Zhai
Shuai Wang
Wenwen Li
Shoukai Wang
Yuqing Su
Wanyue Li
Changzheng Zhu
Wenkang Wang
Yuanxiang Lu
Wentao Li
author_facet Zhiyuan Zhang
Jiaru Gao
Linjiao Jia
Shuxin Kong
Maosen Zhai
Shuai Wang
Wenwen Li
Shoukai Wang
Yuqing Su
Wanyue Li
Changzheng Zhu
Wenkang Wang
Yuanxiang Lu
Wentao Li
author_sort Zhiyuan Zhang
collection DOAJ
description Abstract Background We aim to explore the impact of excessive glutathione (GSH) intake on chemotherapy sensitivity in breast cancer. Methods Clinicopathological data were collected from 460 breast cancer patients who underwent adjuvant chemotherapy from January 2016 to December 2019 from Zhengzhou University People’s Hospital. The clinicopathological characteristics following GSH treatment were collected and compared with those in Non-GSH group after 1:2 propensity score matching (PSM). Intracellular GSH levels and the expression of antioxidant enzymes (NRF2, GPX4 and SOD1) were evaluated in tumor tissues in 51 patients receiving neoadjuvant chemotherapy. Results The recurrence rate after adjuvant chemotherapy was significantly higher in the GSH group (n = 28, 31.8%) than that in the Non-GSH group (n = 39, 22.2%; P = 0.010). Additionally, patients in the HGSH group (high GSH intake, ≥ 16 days) exhibited an elevated recurrence rate compared to that in the LGSH group (low GSH intake, < 16 days) (n = 15 (46.8%) vs. n = 52 (22.4%); P = 0.003). Cox regression revealed that High GSH intake, Ki67 ≥ 30%, Triple negative and Lymphovascular invasion were independent risk factors of progression after adjuvant chemotherapy. Among patients receiving neoadjuvant chemotherapy, intracellular GSH levels and the expression levels of antioxidant enzymes (NRF2, GPX4 and SOD1) in the resistant patients were substantially higher (P < 0.001). Conclusions Excessive GSH intake may contribute to chemotherapy resistance in breast cancer, and the levels of intracellular GSH and antioxidant enzymes are elevated in resistant patients after neoadjuvant chemotherapy, indicating that the standardization of GSH intake may assist in reducing chemotherapy resistance.
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spelling doaj-art-df4be2a7c3d3423491ac38f602f9b5cc2025-08-20T02:39:50ZengBMCWorld Journal of Surgical Oncology1477-78192024-12-0122111910.1186/s12957-024-03626-9Excessive glutathione intake contributes to chemotherapy resistance in breast cancer: a propensity score matching analysisZhiyuan Zhang0Jiaru Gao1Linjiao Jia2Shuxin Kong3Maosen Zhai4Shuai Wang5Wenwen Li6Shoukai Wang7Yuqing Su8Wanyue Li9Changzheng Zhu10Wenkang Wang11Yuanxiang Lu12Wentao Li13Department of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Radiology, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalDepartment of Breast Surgery, Henan Provincial People’s Hospital, Zhengzhou University People’s HospitalAbstract Background We aim to explore the impact of excessive glutathione (GSH) intake on chemotherapy sensitivity in breast cancer. Methods Clinicopathological data were collected from 460 breast cancer patients who underwent adjuvant chemotherapy from January 2016 to December 2019 from Zhengzhou University People’s Hospital. The clinicopathological characteristics following GSH treatment were collected and compared with those in Non-GSH group after 1:2 propensity score matching (PSM). Intracellular GSH levels and the expression of antioxidant enzymes (NRF2, GPX4 and SOD1) were evaluated in tumor tissues in 51 patients receiving neoadjuvant chemotherapy. Results The recurrence rate after adjuvant chemotherapy was significantly higher in the GSH group (n = 28, 31.8%) than that in the Non-GSH group (n = 39, 22.2%; P = 0.010). Additionally, patients in the HGSH group (high GSH intake, ≥ 16 days) exhibited an elevated recurrence rate compared to that in the LGSH group (low GSH intake, < 16 days) (n = 15 (46.8%) vs. n = 52 (22.4%); P = 0.003). Cox regression revealed that High GSH intake, Ki67 ≥ 30%, Triple negative and Lymphovascular invasion were independent risk factors of progression after adjuvant chemotherapy. Among patients receiving neoadjuvant chemotherapy, intracellular GSH levels and the expression levels of antioxidant enzymes (NRF2, GPX4 and SOD1) in the resistant patients were substantially higher (P < 0.001). Conclusions Excessive GSH intake may contribute to chemotherapy resistance in breast cancer, and the levels of intracellular GSH and antioxidant enzymes are elevated in resistant patients after neoadjuvant chemotherapy, indicating that the standardization of GSH intake may assist in reducing chemotherapy resistance.https://doi.org/10.1186/s12957-024-03626-9GlutathioneBreast cancerChemotherapy resistancePrognosticPropensity score matching
spellingShingle Zhiyuan Zhang
Jiaru Gao
Linjiao Jia
Shuxin Kong
Maosen Zhai
Shuai Wang
Wenwen Li
Shoukai Wang
Yuqing Su
Wanyue Li
Changzheng Zhu
Wenkang Wang
Yuanxiang Lu
Wentao Li
Excessive glutathione intake contributes to chemotherapy resistance in breast cancer: a propensity score matching analysis
World Journal of Surgical Oncology
Glutathione
Breast cancer
Chemotherapy resistance
Prognostic
Propensity score matching
title Excessive glutathione intake contributes to chemotherapy resistance in breast cancer: a propensity score matching analysis
title_full Excessive glutathione intake contributes to chemotherapy resistance in breast cancer: a propensity score matching analysis
title_fullStr Excessive glutathione intake contributes to chemotherapy resistance in breast cancer: a propensity score matching analysis
title_full_unstemmed Excessive glutathione intake contributes to chemotherapy resistance in breast cancer: a propensity score matching analysis
title_short Excessive glutathione intake contributes to chemotherapy resistance in breast cancer: a propensity score matching analysis
title_sort excessive glutathione intake contributes to chemotherapy resistance in breast cancer a propensity score matching analysis
topic Glutathione
Breast cancer
Chemotherapy resistance
Prognostic
Propensity score matching
url https://doi.org/10.1186/s12957-024-03626-9
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