| 摘要: |
| ［摘要］ 目的 评估铁死亡相关可变剪接事件预测胃癌预后的价值，并探讨其对肿瘤微环境及治疗反应的影响。方法 基于TCGA数据库的胃癌转录组数据，筛选与铁死亡相关的可变剪接事件，基于LASSO回归和多因素Cox回归构建预后的列线图预测模型。结合功能富集分析、免疫细胞浸润评估及体外实验，验证模型的预测能力及其潜在机制。结果 最终确定由12个铁死亡相关可变剪接事件构建预后预测模型，根据中位风险评分将患者分为高风险组（203例）和低风险组（203例）。低风险组呈现免疫激活特征，预后显著改善（P<0.05），并更可能从靶向治疗和免疫治疗中获益。体外实验证实，剪接因子SF3A2高表达可通过抑制铁死亡促进细胞增殖。结论 铁死亡相关可变剪接事件对胃癌预后和治疗反应的预测效能良好，为制订个体化治疗策略提供了潜在依据。 |
| 关键词: 铁死亡 胃癌 预后 可变剪接 肿瘤微环境 |
| DOI：10.3969/j.issn.1674-3806.2025.09.09 |
| 分类号:R 735.2 |
| 基金项目:国家重点研发计划项目（编号：2023YFC2412005）；北京大学医学青年培育基金项目（编号：BMU2025YFJHPY023） |
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| Study on predictive value of ferroptosis-related alternative splicing events for the prognosis and treatment response of gastric cancer |
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LI Zhiyong, LI Yuxi*, GUO Lei, FAN Xiaopeng, GUO Peng
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Department of Emergency Surgery, Peking University People′s Hospital, Beijing 100044, China
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| Abstract: |
| ［Abstract］ Objective To evaluate the value of ferroptosis-related alternative splicing events in predicting the prognosis of gastric cancer and to explore their impacts on the tumor microenvironment and response to the treatment. Methods Based on the transcriptome data of gastric cancer from The Cancer Genome Atlas(TCGA) database, ferroptosis-related alternative splicing events were screened. A nomogram model for predicting the prognosis of gastric cancer was constructed using LASSO regression and multivariate Cox regression. The predictive ability of the model and its underlying mechanisms were verified by combining functional enrichment analysis, assessment of immune cell infiltration and in vitro experiments. Results It was finally determined that a nomogram model for predicting the prognosis of gastric cancer was constructed based on 12 alternative splicing events related to ferroptosis. According to the median risk scores, the patients were divided into high-risk group(203 patients) and low-risk group(203 patients). The low-risk group exhibited the characteristics of immune activation, with a significantly improved prognosis(P<0.05), and was more likely to benefit from targeted therapy and immunotherapy. The in vitro experiments confirmed that the high expression of the splicing factor SF3A2 promoted cell proliferation by inhibiting ferroptosis. Conclusion Ferroptosis-related alternative splicing events have good efficiency in predicting the prognosis and treatment response of gastric cancer, providing a potential basis for formulating individualized treatment strategies. |
Key words: Ferroptosis Gastric cancer Prognosis Alternative splicing Tumor microenvironment
*共同第一作者 |
