AML 中的 MT1E:了解调节性细胞死亡和免疫治疗反应的途径。

IF 3.6 3区 医学 Q3 CELL BIOLOGY
Xin Zhuang, Peng Chen, Kaiqian Yang, Rong Yang, Xiaoying Man, Ruochen Wang, Yifen Shi
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引用次数: 0

摘要

调节性细胞死亡(RCD)在肿瘤,尤其是急性髓性白血病(AML)的发生和发展中起着至关重要的作用。本研究调查了RCD相关基因在急性髓性白血病预后中的重要性及其与免疫浸润的相关性。我们结合了TCGA和GTEx数据,分析了1488个RCD相关基因,利用LASSO回归和生存分析建立了一个预测模型。我们结合 TCGA 和 GTEx 数据,分析了 1488 个 RCD 相关基因,利用 LASSO 回归和生存分析建立了预测模型,并通过多个数据库验证了模型的准确性,研究了不同风险组的免疫细胞浸润、治疗反应和药物敏感性。RT-qPCR 证实了 MT1E 在急性髓细胞白血病患者和健康骨髓中的表达。我们使用 10 种 RCD 方法建立了一个预后模型,该模型具有很强的预测能力,显示年龄和风险评分与 AML 患者的存活率呈反相关。该模型的功能富集分析与免疫调节通路有关。RT-qPCR 显示,急性髓细胞性白血病与健康骨髓相比,MT1E 的表达量明显较低(p
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MT1E in AML: a gateway to understanding regulatory cell death and immunotherapeutic responses.

Regulated cell death (RCD) plays a crucial role in the initiation and progression of tumors, particularly in acute myeloid leukemia (AML). This study investigates the prognostic importance of RCD-related genes in AML and their correlation with immune infiltration. We combined TCGA and GTEx data, analyzing 1,488 RCD-related genes, to develop a predictive model using LASSO regression and survival analysis. The model's accuracy was validated against multiple databases, examining immune cell infiltration, therapy responses, and drug sensitivity among risk groups. RT-qPCR confirmed MT1E expression in AML patients and healthy bone marrow. CCK8 and Transwell assays measured cell proliferation, adhesion, migration, and invasion, while flow cytometry and Western blotting assessed apoptosis and protein expression. We developed a prognostic model using 10 RCD methods, which demonstrated strong predictive ability, showing an inverse correlation between age and risk scores with survival in AML patients. Functional enrichment analysis of the model is linked to immune modulation pathways. RT-qPCR revealed significantly lower MT1E expression in AML vs healthy bone marrow (P < 0.05). Consequently, experiments were designed to assess the function of MT1E overexpression. Findings indicated that MT1E overexpression showed it significantly reduced THP-1 cell proliferation and adhesion (P < 0.001), decreased migration (P < 0.001), and invasiveness (P < 0.05), and increased apoptosis (P < 0.05), with a notable rise in Caspase3 expression. A novel AML RCD risk model was developed, showing promise as a prognostic marker for evaluating outcomes and immune therapy effectiveness. Insights into MT1E's impact on AML cell proliferation and apoptosis open possibilities for improving patient outcomes and devising personalized treatment strategies.

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来源期刊
Journal of Leukocyte Biology
Journal of Leukocyte Biology 医学-免疫学
CiteScore
11.50
自引率
0.00%
发文量
358
审稿时长
2 months
期刊介绍: JLB is a peer-reviewed, academic journal published by the Society for Leukocyte Biology for its members and the community of immunobiologists. The journal publishes papers devoted to the exploration of the cellular and molecular biology of granulocytes, mononuclear phagocytes, lymphocytes, NK cells, and other cells involved in host physiology and defense/resistance against disease. Since all cells in the body can directly or indirectly contribute to the maintenance of the integrity of the organism and restoration of homeostasis through repair, JLB also considers articles involving epithelial, endothelial, fibroblastic, neural, and other somatic cell types participating in host defense. Studies covering pathophysiology, cell development, differentiation and trafficking; fundamental, translational and clinical immunology, inflammation, extracellular mediators and effector molecules; receptors, signal transduction and genes are considered relevant. Research articles and reviews that provide a novel understanding in any of these fields are given priority as well as technical advances related to leukocyte research methods.
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