黄芪颗粒调节胃癌组织铁死亡相关基因表达及免疫功能的临床研究

Clinical study of Astragalus granules regulating ferroptosis-related gene expression and immune function in gastric cancer tissue

关键词:  黄芪颗粒  胃癌  奥沙利铂  亚叶酸钙  5-氟尿嘧啶方案  信迪利单抗  铁死亡  免疫功能

Key words:  Astragalus granules  gastric cancer  oxaliplatin  leucovorin  5-fluorouracil regimen  sintilimab  ferroptosis  immune function

摘要:

[目的] 探讨黄芪颗粒在晚期胃癌（GC）患者接受奥沙利铂+亚叶酸钙+5-氟尿嘧啶方案（FOLFOX4）联合信迪利单抗（SIN）治疗中的辅助作用，分析其对免疫功能及铁死亡相关基因预后指数（FRGPI）的影响。[方法] 选取2020年1月—2024年12月在邯郸市中心医院住院的223例晚期GC患者，采用随机数字表法分为观察组（111例）和对照组（112例）。对照组接受FOLFOX4方案联合SIN治疗，观察组在此基础上加用黄芪颗粒。治疗周期为3周，均完成至少2个周期。比较两组患者近期疗效客观缓解率（ORR）、免疫功能（CD3⁺、CD4⁺、CD8⁺百分比）、铁死亡相关基因表达（FRGPI）及不良反应情况。[结果] 观察组ORR为52.2%，对照组为34.9%，差异具有统计学意义（P<0.05）。治疗后，两组CD3⁺和CD4⁺水平均较治疗前升高（P<0.05），CD8⁺水平降低（P<0.05）；观察组改善幅度优于对照组（P<0.05）。治疗后两组FRGPI水平均较治疗前降低（P<0.05），且观察组下降更加显著（P<0.05）。Pearson分析显示，CD3⁺和CD4⁺与FRGPI呈负相关（P<0.01），CD8⁺与FRGPI呈正相关（P<0.01）。不良反应方面，观察组恶心呕吐、白细胞减少及肝肾功能损害的发生率均低于对照组（P<0.05），而血小板减少和手足综合征发生率比较，差异无统计学意义（P>0.05）。[结论] 黄芪颗粒联合FOLFOX4+SIN治疗可以显著提高晚期GC患者的近期疗效，改善免疫功能，降低FRGPI水平，并减轻部分治疗相关毒副作用。其作用机制可能与调控铁死亡过程及改善免疫微环境有关，为黄芪颗粒作为免疫化学治疗辅助治疗提供了临床依据。

Abstract:

[Objective] To investigate the adjuvant effects of Astragalus granules in patients with advanced gastric cancer（GC）receiving the oxaliplatin + leucovorin + 5-fluorouracil regimen（FOLFOX4）combined with sintilimab （SIN），and to evaluate their impact on immune function and the ferroptosis-related gene prognostic index（FRGPI）. [Methods] A total of 223 patients with advanced GC admitted to our hospital between January 2020 and December 2024 were enrolled and randomly assigned to an observation group（n=111）or a control group（n=112）using a random number table. The control group received the FOLFOX4 regimen plus SIN，while the observation group received additional Astragalus granules on this basis. Each treatment cycle lasted 3 weeks，and all patients completed at least 2 cycles. Short-term efficacy [objective response rate（ORR）]，immune function（percentages of CD3⁺，CD4⁺，and CD8⁺ T cells），FRGPI levels，and adverse reactions were compared between the two groups. [Results] The ORR was significantly higher in the observation group（52.2%）than in the control group（34.9%）（P<0.05）. After treatment，CD3⁺ and CD4⁺ levels increased and CD8⁺ levels decreased in both groups（all P<0.05），with greater changes observed in the observation group（P<0.05）. FRGPI levels were reduced in both groups after treatment（P< 0.05），with a more pronounced decrease in the observation group（P<0.05）. Pearson correlation analysis showed that CD3⁺ and CD4⁺ were negatively correlated with FRGPI（P<0.01），while CD8⁺ was positively correlated with FRGPI（P<0.01）. The incidence of nausea/ vomiting，leukopenia，and hepatic/renal impairment was lower in the observation group than in the control group（P<0.05），whereas the incidence of thrombocytopenia and hand foot syndrome showed no significant differences between the two groups（P>0.05）. [Conclusion] Astragalus granules combined with FOLFOX4 and sintilimab significantly improved short-term efficacy in patients with advanced gastric cancer，enhanced immune function，reduced FRGPI levels，and alleviated certain treatment-related toxicities. These effects may be associated with the regulation of ferroptosis and improvement of the immune microenvironment， providing clinical evidence for the use of Astragalus granules as an adjuvant to immunochemotherapy.