Song Yinsen, Yang Zhenzhen, Gao Na, Zhang Bojun
Translational Medicine Research Center (Key Laboratory of Organ Transplantation of Henan Province), The Fifth Clinical Medical College of Henan University of Chinese Medicine (Zhengzhou People's Hospital), Zhengzhou, China.
Department of Pathogenic Microbiology and Immunology, School of Basic Medical Sciences, Xi'an Jiaotong University, No.76 Yanta West Road, Xi'an, China.
Discov Oncol. 2024 Jul 12;15(1):279. doi: 10.1007/s12672-024-01150-6.
Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has a poor prognosis and a high rate of relapse. Dysregulated metabolism plays an important role in AML progression. This study aimed to conduct a comprehensive analysis of MRGs using TCGA and GEO datasets and further explore the potential function of critical MRGs in AML progression. In this study, we identified 17 survival-related differentially expressed MRGs in AML using TCGA and GEO datasets. The 150 AML samples were divided into three molecular subtypes using 17 MRGs, and we found that three molecular subtypes exhibited a different association with ferroptosis, cuproptosis and m6A related genes. Moreover, a prognostic signature that comprised nine MRGs and had good predictive capacity was established by LASSO-Cox stepwise regression analysis. Among the 17 MRGs, our attention focused on MICAL1 which was highly expressed in many types of tumors, including AML and its overexpression was also confirmed in several AML cell lines. We also found that the expression of MICAL1 was associated with several immune cells. Moreover, functional experiments revealed that knockdown of MICAL1 distinctly suppressed the proliferation of AML cells. Overall, this study not only contributes to a deeper understanding of the molecular mechanisms underlying AML but also provides potential targets and prognostic markers for AML treatment. These findings offer robust support for further research into therapeutic strategies and mechanisms related to AML, with the potential to improve the prognosis and quality of life for AML patients. Nevertheless, further research is needed to validate these findings and explore more in-depth molecular mechanisms.
急性髓系白血病(AML)是最常见的造血系统恶性肿瘤之一,预后较差且复发率高。代谢失调在AML进展中起重要作用。本研究旨在利用TCGA和GEO数据集对代谢相关基因(MRGs)进行综合分析,并进一步探索关键MRGs在AML进展中的潜在功能。在本研究中,我们利用TCGA和GEO数据集在AML中鉴定出17个与生存相关的差异表达MRGs。使用这17个MRGs将150例AML样本分为三种分子亚型,我们发现三种分子亚型与铁死亡、铜死亡和m6A相关基因表现出不同的关联。此外,通过LASSO-Cox逐步回归分析建立了一个由9个MRGs组成且具有良好预测能力的预后特征。在这17个MRGs中,我们将注意力集中在MICAL1上,它在包括AML在内的多种肿瘤类型中高表达,并且在几种AML细胞系中也证实了其过表达。我们还发现MICAL1的表达与几种免疫细胞有关。此外,功能实验表明,敲低MICAL1可明显抑制AML细胞的增殖。总体而言,本研究不仅有助于更深入地了解AML的分子机制,还为AML治疗提供了潜在的靶点和预后标志物。这些发现为进一步研究AML相关的治疗策略和机制提供了有力支持,有可能改善AML患者的预后和生活质量。然而,需要进一步的研究来验证这些发现并探索更深入的分子机制。