Department of Hematological Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng East Road, 510060 Guangzhou, Guangdong, China.
Department of Pathology, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Int Immunopharmacol. 2022 Jul;108:108802. doi: 10.1016/j.intimp.2022.108802. Epub 2022 May 13.
Acutemyeloidleukaemia(AML) is an illness of varied origin and unpredictable prognosis. Pyroptosis, a novel class of gasdermin-mediated programmed cell death (PCD), serves a critical function in anti-leukemia. But, the correlation between pyroptosis-related genes (PRGs) and AML prognosis is undetermined. Here, we obtained the RNA profile and matched clinical information of AML patients from the TCGA and GEO databases. 6 PRGs were identified to be strongly related to AML prognosis via univariate COX analysis. Next, the LASSO regression analysis was used to develop a PRG signature for AML prognosis, which was then employed for the stratification of patients into a low- (LR) or high-risk (HR) group. Kaplan-Meier analysis revealed that the HR group, but not the LR group, had worse prognosis. In addition, ROC curve analysis revealed that our prognotic model had good predictive value. Functional enrichment analysis indicated that the immune status was remarkably different between the two risk groups. In vitro experiments demonstrated that pyroptosis serves an essential function in anti-leukemia treatment. In summary, our newly developed model has good predictive value and can offer guidance into the precise estimation of AML prognosis and targeting pyroptosis is a potential therapeutic alternative for AML.
急性髓系白血病(AML)是一种起源和预后不可预测的疾病。细胞焦亡,一种新型的 Gasdermin 介导的程序性细胞死亡(PCD),在抗白血病中发挥着关键作用。但是,细胞焦亡相关基因(PRGs)与 AML 预后的相关性尚未确定。在这里,我们从 TCGA 和 GEO 数据库中获得了 AML 患者的 RNA 图谱和匹配的临床信息。通过单因素 COX 分析,确定了 6 个与 AML 预后密切相关的 PRGs。接下来,使用 LASSO 回归分析为 AML 预后建立了 PRG 特征,并将患者分为低风险(LR)或高风险(HR)组。Kaplan-Meier 分析表明,HR 组而非 LR 组预后更差。此外,ROC 曲线分析表明,我们的预后模型具有良好的预测价值。功能富集分析表明,两组之间的免疫状态存在显著差异。体外实验表明,细胞焦亡在抗白血病治疗中起着重要作用。总之,我们新开发的模型具有良好的预测价值,可以为 AML 预后的精确评估提供指导,靶向细胞焦亡是 AML 的一种潜在治疗选择。