Bin Ting, Tang Jing, Lu Bo, Xu Xiao-Jun, Lin Chao, Wang Ying
Department of Haematology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518000, China.
Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518000, China.
Ann Hematol. 2024 Dec;103(12):5297-5314. doi: 10.1007/s00277-024-06119-7. Epub 2024 Nov 28.
Acute myeloid leukaemia (AML) was originally an aggressive malignancy of the bone marrow and one of the deadliest forms of acute leukaemia. The 5-year mortality benefit for patients with AML was only 28.3%. Moreover, a large proportion of patients experienced frequent relapses even after remission, thus predicting a bleak prognosis. This research employed differential expression analysis of AML and normal samples sourced from the GSE30029 database, as well as weighted gene co-expression network analysis (WGCNA). We discovered differential golgi apparatus-related genes (DGARGs) specifically associated with AML. Via regressivity analysis and machine learning algorithm, the cancer genome atlas-acute myeloid leukemia (TCGA-AML) cohort developed a prognostic model using characteristic prognostic genes. The performance value of risk score was analysed using Kaplan-Meier (KM) curves and Cox regression. A predictive nomogram was developed to assess the outcome. The association between prognostic trait genes and the immune microenvironment was examined. Finally, immunoactivity and drug susceptibilities were evaluated in various risk groups identified by prognostic signature genes. A total of 77 DGARGs were obtained by differential expression analysis with WGCNA analysis. Following univariate Cox regression and LASSO regression, six prognostic signature genes (ARL5B, GALNT12, MANSC1, PDE4DIP, NCALD and CYP2E1) were utilized to develop a prognostic model. This model was calibrated via KM survival and receiver operating characteristic (ROC) curves, which concluded that it had a predictive impact on the prognosis of AML. Further analysis of the tumour microenvironment in AML patients demonstrated notable variances in immune cell APC_co_inhibition, CCR, Parainflammation, Type_I_IFN_Response, and Type_II_IFN_Response between the high-risk and low-risk groups. A prognostic model was devised in this study using six prognostic genes linked to the Golgi apparatus. The exactness of the model in guiding the prognosis of AML was established. As a result of expression validation, CYP2E1 and GALNT12 will be used as biomarkers to offer fresh insights into the prognosis and treatment of AML patients.
急性髓系白血病(AML)最初是一种侵袭性骨髓恶性肿瘤,也是最致命的急性白血病形式之一。AML患者的5年生存率仅为28.3%。此外,即使在缓解后,很大一部分患者仍频繁复发,因此预后不佳。本研究采用来自GSE30029数据库的AML样本和正常样本进行差异表达分析,以及加权基因共表达网络分析(WGCNA)。我们发现了与AML特异性相关的差异高尔基体相关基因(DGARGs)。通过回归分析和机器学习算法,癌症基因组图谱 - 急性髓系白血病(TCGA - AML)队列使用特征性预后基因建立了一个预后模型。使用Kaplan - Meier(KM)曲线和Cox回归分析风险评分的性能值。开发了一个预测列线图来评估结果。研究了预后特征基因与免疫微环境之间的关联。最后,在由预后特征基因确定的不同风险组中评估免疫活性和药物敏感性。通过WGCNA分析进行差异表达分析,共获得77个DGARGs。经过单变量Cox回归和LASSO回归后,利用六个预后特征基因(ARL5B、GALNT12、MANSC1、PDE4DIP、NCALD和CYP2E1)建立了一个预后模型。该模型通过KM生存曲线和受试者工作特征(ROC)曲线进行校准,结果表明它对AML的预后具有预测作用。对AML患者肿瘤微环境的进一步分析表明,高风险组和低风险组之间在免疫细胞APC_co_inhibition、CCR、副炎症、I型干扰素反应和II型干扰素反应方面存在显著差异。本研究使用与高尔基体相关的六个预后基因设计了一个预后模型。确定了该模型在指导AML预后方面的准确性。通过表达验证,CYP2E1和GALNT12将用作生物标志物,为AML患者的预后和治疗提供新的见解。