急性髓系白血病基底膜相关预后模型的建立及肿瘤微环境浸润的表征。

IF 3.3 3区 医学 Q2 ONCOLOGY
Journal of Cancer Pub Date : 2025-01-13 eCollection Date: 2025-01-01 DOI:10.7150/jca.108041
Zongsi Zhu, Yuedong Zhao, Ping Li
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引用次数: 0

摘要

背景:基底膜是上皮和内皮组织细胞外基质的特殊成分,能维持上皮和内皮组织的正常形态和功能。它还可以参与肿瘤的进展,影响肿瘤的治疗。然而,基底膜相关基因(bmg)在急性髓性白血病(AML)中的作用尚不清楚。材料和方法:我们从TCGA、GTEx和GEO下载AML和正常样本的数据。然后,我们进行了生物信息学分析,以确定不同的bmg。我们计算了培训队列的风险评分,并将其分为两个风险组。此外,我们还引入了外部队列作为验证队列,以估计风险评分的准确性。根据风险评分和临床病理特征建立nomogram预测预后。根据BMGs, TCGA AML患者可分为2个亚型。为了研究免疫细胞与TME之间的生物学特性和关系,我们利用GSVA来评估途径富集,利用ssGSEA来量化免疫细胞浸润水平。结果:我们获得了AML与正常样本之间的3个差异BMGs。培训队列根据风险评分分为高风险组和低风险组。Kaplan-Meier生存分析显示两组有显著差异。该图可用于预测AML患者的生存结局。根据聚类结果,我们发现两个基因簇之间存在显著差异。Sankey的图表显示B类与高危人群和预后不良相关。GSVA分析显示,簇B也与细胞间和细胞内信号转导通路的上调有关。在TME中,高危组静息肥大细胞、滤泡辅助性T细胞和浆细胞减少,单核细胞增加。此外,高危组对BTK和AKT抑制剂更为敏感。结论:BMGs的nomogram模型可以预测AML患者的预后。同时,BMGs与AML免疫TME相关。正确和全面地评估个体的bmg机制将有助于指导更有效的治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Establishment of a Basement Membrane-Related Prognosis Model and Characterization of Tumor Microenvironment Infiltration in Acute Myeloid Leukemia.

Background: Basement membrane is a special component of extracellular matrix of epithelial and endothelial tissues, which can maintain their normal morphologies and functions. It can also participate in tumor progression and affect tumor treatment. However, the roles of basement membrane-related genes (BMGs) in acute myeloid leukemia (AML) remain unknown. Material and methods: We downloaded the data of AML and normal samples from TCGA, GTEx, and GEO. Then, we performed bioinformatics analysis to identify differential BMGs. We calculated the risk score of the training cohort and divided it into two risk groups. In addition, we also introduced external cohorts, serving as validation cohorts, to estimate the accuracy of risk score. A nomogram was established based on the risk score and clinicopathological characteristics to predict the prognosis. Based on BMGs, AML patients of TCGA were clustered into 2 subtypes. To investigate the biological features and the association between immune cells and TME, we utilized GSVA to assess pathway enrichment and ssGSEA to quantify the levels of immune cell infiltration across samples. Results: We obtained 3 differential BMGs between AML and normal samples. The training cohort was divided into high- and low-risk groups based on the risk score. The Kaplan-Meier survival analysis indicated that the two groups had significant differences. The nomogram could be used to predict the survival outcomes of AML patients. Based on the clustering result, we found significant differences between the two gene clusters. Sankey's diagram suggested that cluster B was associated with the high-risk group and poor prognosis. GSVA analysis showed that cluster B was also related to the upregulation of intercellular and intracellular signal transduction pathways. In TME, resting mast cells, follicular helper T cells, and plasma cells decreased while monocytes increased in the high-risk group. In addition, the high-risk group was more sensitive to BTK and AKT inhibitors. Conclusion: Our study indicated that the nomogram model of BMGs could predict the prognosis of AML patients. Meanwhile, BMGs were correlated with immune TME in AML. A correct and comprehensive assessment of the mechanisms of BMGs in individuals will help guide more effective treatment.

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来源期刊
Journal of Cancer
Journal of Cancer ONCOLOGY-
CiteScore
8.10
自引率
2.60%
发文量
333
审稿时长
12 weeks
期刊介绍: Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
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