Potential value of immunogenic cell death related-genes in refining European leukemiaNet guidelines classification and predicting the immune infiltration landscape in acute myeloid leukemia.

IF 5.3 2区医学 Q1 ONCOLOGY

Cancer Cell International Pub Date : 2025-02-18 DOI:10.1186/s12935-025-03670-9

Changqing Jiao, Xiaoyu Ma, Jianling Cui, Bobin Su, Fei Xu, Enbo Chen, Junjie Zhou, Jifei Dai, Mengya Pan, Zhangbiao Long, Jian Ge

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Abstract

Immunogenic cell death (ICD) is the kind of cell death that triggers the immune system. It affects several tumors, whereas its significance for prognosis in acute myeloid leukemia (AML) remains uncertain. AML categorization by cytogenetic variables is inaccurate. In addition, risk stratification of AML based on cytogenetics is imprecise. The data of AML patients were extracted from 4 databases, a total of 1,537 patients. Univariate and LASSO Cox regression analyses were conducted to construct an ICD risk signature (ICDRS). The ICDRS showed strong prognostic value for AML through Kaplan-Meier, Cox, ROC analyses and nomogram. Combining the ICDRS with the European LeukemiaNet (ELN) classification to redefine the risk stratification can better predict the prognosis of AML. Moreover, the ICDRS was examined to identify gene functional enrichment, immunological characteristics, drug susceptibility, and somatic mutation, which revealed considerable variations among different risk categories. We further validated the expression of ICDRS in the AML bone marrow microenvironment by single-cell RNA (scRNA) analysis. Ultimately, the functional role of CASP1 was proven in AML by a series of in-vitro experiments. Our study highlights the significant impact of ICDRS on AML, which may improve ELN risk classification, predict immune landscapes, and guide personalized therapy.

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免疫原性细胞死亡相关基因在完善欧洲白血病网络指南分类和预测急性髓性白血病免疫浸润景观中的潜在价值

免疫原性细胞死亡（ICD）是一种触发免疫系统的细胞死亡。它影响多种肿瘤，但其对急性髓性白血病（AML）预后的意义尚不确定。AML的细胞遗传学变量分类是不准确的。此外，基于细胞遗传学的AML风险分层是不精确的。AML患者数据提取自4个数据库，共1537例患者。采用单变量和LASSO Cox回归分析构建ICD风险特征（ICDRS）。通过Kaplan-Meier、Cox、ROC分析和nomogram分析，ICDRS对AML具有较强的预后价值。将ICDRS与欧洲白血病网（ELN）分级相结合，重新定义风险分层，可以更好地预测AML的预后。此外，对ICDRS进行了基因功能富集、免疫学特征、药物敏感性和体细胞突变的检测，发现不同风险类别之间存在相当大的差异。我们通过单细胞RNA （scRNA）分析进一步验证了ICDRS在AML骨髓微环境中的表达。最终，通过一系列体外实验证实了CASP1在AML中的功能作用。我们的研究强调了ICDRS对AML的重要影响，可以改善ELN风险分类，预测免疫景观，指导个性化治疗。

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来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.