Objective: To explore the role of ferroptosis-related genes in multiple myeloma(MM) through TCGA database and FerrDb, and build a prognostic model of ferroptosis-related genes for MM patients.
Methods: Using the TCGA database containing clinical information and gene expression profile data of 764 patients with MM and the FerrDb database including ferroptosis-related genes, the differentially expressed ferroptosis-related genes were screened by wilcox.test function. The prognostic model of ferroptosis-related genes was established by Lasso regression, and the Kaplan-Meier survival curve was drawn. Then COX regression analysis was used to screen independent prognostic factors. Finally, the differential genes between high-risk and low-risk patients were screened, and enrichment analysis was used to explore the mechanism of the relationship between ferroptosis and prognosis in MM.
Results: 36 differential genes related to ferroptosis were screened out from bone marrow samples of 764 MM patients and 4 normal people, including 12 up-regulated genes and 24 down-regulated genes. Six prognosis-related genes (GCLM, GLS2, SLC7A11, AIFM2, ACO1, G6PD) were screened out by Lasso regression and the prognostic model with ferroptosis-related genes of MM was established. Kaplan-Meier survival curve analysis showed that the survival rate between high risk group and low risk group was significantly different(P<0.01). Univariate COX regression analysis showed that age, sex, ISS stage and risk score were significantly correlated with overall survival of MM patients(P<0.05), while multivariate COX regression analysis showed that age, ISS stage and risk score were independent prognostic indicators for MM patients (P<0.05). GO and KEGG enrichment analysis showed that the ferroptosis-related genes was mainly related to neutrophil degranulation and migration, cytokine activity and regulation, cell component, antigen processing and presentation, complement and coagulation cascades, haematopoietic cell lineage and so on, which may affect the prognosis of patients.
Conclusion: Ferroptosis-related genes change significantly during the pathogenesis of MM. The prognostic model of ferroptosis-related genes can be used to predict the survival of MM patients, but the mechanism of the potential function of ferroptosis-related genes needs to be confirmed by further clinical studies.
题目: 多发性骨髓瘤铁死亡相关组学分析及预后模型的建立.
目的: 通过TCGA及FerrDb数据库探讨铁死亡相关基因在多发性骨髓瘤（MM）中的作用，并构建MM相关铁死亡基因预后模型。.
方法: 利用包含764例MM患者临床信息及基因表达谱数据的TCGA数据库与包括铁死亡相关基因的FerrDb数据库，通过wilcox.test函数筛选其中的差异表达铁死亡相关基因。应用Lasso回归建立铁死亡相关基因预后模型，并绘制Kaplan-Meier生存曲线。使用COX回归分析筛选独立预后因素。筛选不同风险患者组间的差异基因，并通过富集分析探究MM铁死亡与预后相关的组学机制。.
结果: 通过对764例MM患者骨髓样本及4例正常人骨髓样本进行差异分析，共筛选出铁死亡相关差异基因36个，其中上调基因12个，下调基因24个。使用Lasso回归筛选出6个预后相关基因（GCLM、GLS2、SLC7A11、AIFM2、ACO1、G6PD）并建立了MM铁死亡相关基因预后模型；Kaplan-Meier生存曲线分析结果显示，不同风险患者组间生存率具有显著统计学差异（P<0.01）。单因素COX回归分析结果显示，年龄、性别、ISS分期和风险评分与MM患者总生存期（OS）显著相关（P<0.05）；多因素COX回归分析表明，年龄、ISS分期和风险评分是MM患者OS的独立预后指标（P<0.05）。GO与KEGG富集分析显示，铁死亡相关基因可能通过中性粒细胞的趋化与迁移、细胞因子活性及调控、细胞组分、抗原加工提呈、补体及凝血级联反应、造血祖细胞谱系等影响患者预后。.
结论: 铁死亡相关基因在MM发病过程中变化显著，铁死亡相关基因预后模型可用于预测MM患者的生存情况，但铁死亡的潜在功能机制有待进一步临床研究证实。.
Keywords: ferroptosis; multiple myeloma; prognosis model.