铁死亡相关复发风险模型预测胶质母细胞瘤患者的临床结局与免疫浸润  

Ferroptosis-related Recurrence Risk Model Predicts Clinical Outcomes and Immune Infiltration in Glioblastoma

作　　者：廖永珍[1] 梁禄 李意 丛丽[2] LIAO Yongzhen;LIANG Lu;LI Yi;CONG Li(School of Medicine&Health Care,Shunde Polytechnic,Foshan 528300,China;School of Medicine,Hunan Normal University,Changsha 410013,China)

机构地区：[1]顺德职业技术学院医药卫生学院,佛山528300 [2]湖南师范大学医学院,长沙410013

出　　处：《肿瘤防治研究》2023年第3期249-257,共9页Cancer Research on Prevention and Treatment

基　　金：湖南省自然科学基金(2020JJ5381);湖南省卫生健康委科研课题(202103011683);湖南师范大学医学院开放基金(KF2022036)。

摘　　要：目的构建铁死亡相关胶质母细胞瘤(GBM)复发预后风险模型并评价患者预后。方法通过CGGA和FerrDb数据库筛选复发GBM中铁死亡相关差异表达基因,经过Lasso分析构建nomogram模型,并利用TCGA数据验证预测效能。基因本体功能和信号通路富集分析影响患者预后的机制,通过ESTIMATE算法和TIMER数据库研究肿瘤免疫浸润与免疫检测点表达情况。结果WWTR1、PLIN2、BID是GBM复发的重要铁死亡相关基因,结合性别、年龄构建的nomogram校正曲线一致性良好,1、3、5年AUC分别为0.65、0.66、0.63(CGGA)和0.68、0.76、0.79(TCGA)。高风险亚型中上皮间充质转化、KRAS和炎性反应通路活性明显上调(P<0.05),免疫细胞浸润较少(P<0.05),且风险评分与免疫抑制检测点呈正相关(r=0.43~0.57,P<0.05)。结论基于3个铁死亡相关复发风险基因构建预后评分模型,发现浸润性免疫细胞和免疫检测点影响GBM患者预后。Objective To construct a ferroptosis-related glioblastoma(GBM)recurrence risk model and evaluate the prognosis of patients.Methods Differentially expressed genes(DEGs)related to ferroptosis in recurrent GBM were screened by CGGA and FerrDb databases.Key genes were obtained by Lasso regression.Then,nomogram was constructed according to the key risk genes,and the prediction efficiency was verified using the TCGA database.GO,KEGG,and GSEA databases were used in exploring the mechanism of prognosis.ESTIMATE and TIMER were used in studying tumor immune infiltration and the expression of immune check points.Results WWTR1,PLIN2,and BID were important prognostic factors for GBM recurrence.The nomogram was constructed according to gender and age,and the observed values were in good agreement with the predicted values.The AUC values were 0.65(1 year),0.66(3 years),and 0.63(5 years)for CGGA and 0.68(1 year),0.76(3 years),and 0.79(5 years)for TCGA.Epithelial mesenchymal transition,KRAS pathway,and inflammatory response were significantly upregulated in the high-risk subtypes(P<0.05).Immune cell infiltration was lower(P<0.05).Risk score was positively correlated with the expression of immunosuppression check points.Conclusion Ferroptosis-related genes WWTR1,PLIN2,and BID can be used in constructing a nomogram with good predictive performance.These risk genes may affect prognosis through tumor-infiltrating immune cells and immune check points.

关 键 词：胶质母细胞瘤 铁死亡 复发预后风险模型 免疫浸润 

分 类 号：R730.264[医药卫生—肿瘤]