Construction of AML prognostic model with CYP2E1 and GALNT12 biomarkers based on golgi- associated genes.

IF 3 3区 医学 Q2 HEMATOLOGY Annals of Hematology Pub Date : 2024-11-28 DOI:10.1007/s00277-024-06119-7
Ting Bin, Jing Tang, Bo Lu, Xiao-Jun Xu, Chao Lin, Ying Wang
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Abstract

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.

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基于巨球蛋白相关基因,利用 CYP2E1 和 GALNT12 生物标志物构建急性髓细胞性白血病预后模型。
急性髓性白血病(AML)原本是一种侵袭性骨髓恶性肿瘤,也是最致命的急性白血病之一。急性髓细胞白血病患者的 5 年死亡率仅为 28.3%。此外,很大一部分患者即使在病情缓解后也会频繁复发,因此预后不容乐观。本研究采用了来自 GSE30029 数据库的 AML 和正常样本的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 特别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-急性髓性白血病(TCGA-AML)队列利用特征性预后基因建立了一个预后模型。利用卡普兰-迈尔(KM)曲线和考克斯回归分析了风险评分的性能值。开发了一个预测提名图来评估结果。研究还考察了预后性状基因与免疫微环境之间的关联。最后,根据预后特征基因确定的不同风险组别对免疫活性和药物敏感性进行了评估。通过差异表达分析和 WGCNA 分析,共获得 77 个 DGARGs。在进行单变量 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。通过KM生存率和接收者操作特征曲线(ROC)对该模型进行了校准,结果表明该模型对急性髓细胞性白血病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,高危组和低危组的免疫细胞 APC_协同抑制、CCR、副炎、Type_I_IFN_Response 和 Type_II_IFN_Response 存在明显差异。本研究利用与高尔基体相关的六个预后基因设计了一个预后模型。该模型在指导急性髓细胞性白血病预后方面的准确性得以确立。通过表达验证,CYP2E1 和 GALNT12 将被用作生物标志物,为 AML 患者的预后和治疗提供新的见解。
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来源期刊
Annals of Hematology
Annals of Hematology 医学-血液学
CiteScore
5.60
自引率
2.90%
发文量
304
审稿时长
2 months
期刊介绍: Annals of Hematology covers the whole spectrum of clinical and experimental hematology, hemostaseology, blood transfusion, and related aspects of medical oncology, including diagnosis and treatment of leukemias, lymphatic neoplasias and solid tumors, and transplantation of hematopoietic stem cells. Coverage includes general aspects of oncology, molecular biology and immunology as pertinent to problems of human blood disease. The journal is associated with the German Society for Hematology and Medical Oncology, and the Austrian Society for Hematology and Oncology.
期刊最新文献
Concurrent inhibited erythropoiesis in a case of VEXAS syndrome. Application of allogeneic hematopoietic stem cell transplantation to treat Behcet's disease with myelodysplastic syndrome: a case report and literature review. Clonal evolution defines risk stratification for central nervous system leukemia in adult acute lymphoblastic leukemia. Digital PCR (dPCR) is able to anticipate the achievement of stable deep molecular response in adult chronic myeloid leukemia patients: results of the DEMONSTRATE study. Construction of AML prognostic model with CYP2E1 and GALNT12 biomarkers based on golgi- associated genes.
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