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

作者：Zhiyuan Zhang, Jian Gao, Linjiao Jia, Shuxin Kong, Maosen Zhai, Shuai Wang, Wenwen Li, Wenwen Li, Shoukai Wang, Yuqing Su, Wanyue Li, Wanyue Li, Changzheng Zhu, Wenkang Wang, Yuanxiang Lu, Wentao Li, Wentao Li · 发表于：World Journal of Surgical Oncology · 年份：2024 · DOI：10.1186/s12957-024-03626-9 · 被引用次数：14 · 研究领域：Sulfur Compounds in Biology、Glutathione Transferases and Polymorphisms、Redox biology and oxidative stress

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 chemothera...