Shi Jing, Zhao Fuxing, Qiu Tianlei, Ren Dengfeng, Li Zitao, Ma Junli, Zhao Jiuda
School of Clinical Medicine of Qinghai University, Affiliated Hospital of Qinghai University, Xining, 810000, China.
Breast Disease Diagnosis and Treatment Center of Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China.
Discov Oncol. 2025 May 28;16(1):938. doi: 10.1007/s12672-025-02611-2.
The unique hypoxic environment in high-altitude regions is increasingly drawing attention for its impact on the health of residents, particularly in patients post-chemotherapy. This study aimed to investigate the effects and potential mechanisms of high-altitude hypoxia on myelosuppression following chemotherapy, with the goal of providing a theoretical basis for clinical treatment. A retrospective clinical study of 80 patients with breast cancer revealed that patients in the plateau exhibited a significantly higher incidence of grade 3 or higher neutropenia and any level of neutropenia post-chemotherapy than those in the plain, with propensity score matching (PSM) confirming these associations. Animal experiments revealed that high-altitude hypoxia reduced the white blood cell (WBC) count, granulocyte count, lymphocyte count, and number of bone marrow nucleated cells (BMNCs) in cyclophosphamide (CTX)-treated mice. Additionally, high-altitude hypoxia induced a significant reduction in the proliferation index and an elevation in apoptosis rates in BMNCs. High-altitude hypoxia also significantly reduced serum levels of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Transcriptomic analysis of BMNCs demonstrated that high-altitude hypoxia might modulate the hematopoietic function in CTX-induced myelosuppression mice through pathways related to hematopoiesis, such as porphyrin metabolism, hematopoietic cell lineage, ECM-receptor interaction, and PI3K-Akt signaling pathway. Our results suggest that high-altitude hypoxia exacerbates chemotherapy-induced myelosuppression, possibly through reducing the serum level of G-CSF/GM-CSF and regulating apoptosis and proliferation by PI3K-Akt signaling pathway, highlighting that cancer patients undergoing chemotherapy in hypoxic environments may require enhanced supportive care to mitigate these adverse effects.
高海拔地区独特的缺氧环境因其对居民健康的影响，尤其是对化疗后患者的影响，越来越受到关注。本研究旨在探讨高海拔缺氧对化疗后骨髓抑制的影响及潜在机制，为临床治疗提供理论依据。一项对80例乳腺癌患者的回顾性临床研究表明，高原地区患者化疗后3级及以上中性粒细胞减少症和任何程度中性粒细胞减少症的发生率均显著高于平原地区患者，倾向得分匹配（PSM）证实了这些关联。动物实验表明，高海拔缺氧降低了环磷酰胺（CTX）处理小鼠的白细胞（WBC）计数、粒细胞计数、淋巴细胞计数和骨髓有核细胞（BMNC）数量。此外，高海拔缺氧导致BMNC的增殖指数显著降低，凋亡率升高。高海拔缺氧还显著降低了血清粒细胞集落刺激因子（G-CSF）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）水平。对BMNC的转录组分析表明，高海拔缺氧可能通过与造血相关的途径，如卟啉代谢、造血细胞谱系、ECM-受体相互作用和PI3K-Akt信号通路，调节CTX诱导的骨髓抑制小鼠的造血功能。我们的结果表明，高海拔缺氧可能通过降低血清G-CSF/GM-CSF水平并通过PI3K-Akt信号通路调节细胞凋亡和增殖，从而加剧化疗诱导的骨髓抑制，这突出表明在缺氧环境中接受化疗的癌症患者可能需要加强支持治疗以减轻这些不良反应。
