Department of Clinical Laboratory, the First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.
Yunnan Key Laboratory of Laboratory Medicine, Kunming, Yunnan, P.R. China.
Medicine (Baltimore). 2024 May 31;103(22):e38432. doi: 10.1097/MD.0000000000038432.
Acute myeloid leukemia (AML), an uncommonly low 5-year survival and high mortality rate, is a potentially catastrophic diagnosed subtype of leukemia. The development of new prognostic markers is urgently needed to guide its treatment. Necroptosis is a newly defined biological process for regulating cell death, and previous studies have confirmed that the abnormality of the physical function can lead to multiple malignancies. Here, we performed necroptosis-related genes (NRGs) to build a predictive model in the Cancer Genome Atlas (TCGA)-AML patients, thus exploring the correlation between the NRG prognosis signature (NRG score) of this model and immune infiltration, pathway activity, clinical features, and immunotherapy. Besides, we computed the statistical measure Spearman rank correlation between the NRG score and the Log IC50 values of therapeutic agents. Subsequently, we divided the TCGA-AML cohort into 2 groups, one with high scores and the other with low scores depending on the model score. AML patients with high NRG scores exhibited a lower estimated overall survival (OS) rate than those with low NRG scores, which was confirmed in the validation set. The prognostic value of the constructed NRG signature to the AML, independent of other variables, was demonstrated by uni- and multivariate stepwise regression analysis. When comparing the infiltrating states of specialized cells associated with immune system from the 2 groups, B cells naive, Plasma cells, and monocytes represented significant differences among various subgroups of samples. Moreover, the 30 hallmark-related pathways related to necroptosis characteristics were remarkably different between the high/low NRG score groups. And patients showed remarkable NRG score distribution in clinical features of bone marrow lymphocyte, category, and FAB classifications. Besides, we found that the BIRB0796, VX680, Vorinostat, and Axitinib positively related with NRG score, whereas CI. 1040, PD. 0325901, Z.L LNle. CHO, and AZD6244 negatively correlated with the NRG score. These drugs may provide a reference for subsequent treatment.
急性髓细胞白血病（AML）是一种罕见的低 5 年生存率和高死亡率的疾病，是一种潜在的灾难性的白血病亚型。迫切需要开发新的预后标志物来指导其治疗。坏死是一种新定义的调节细胞死亡的生物学过程，先前的研究已经证实，物理功能的异常会导致多种恶性肿瘤。在这里，我们对坏死相关基因（NRGs）进行了分析，以构建一个癌症基因组图谱（TCGA）-AML 患者的预测模型，从而探讨该模型的 NRG 预后特征（NRG 评分）与免疫浸润、途径活性、临床特征和免疫治疗之间的相关性。此外，我们计算了 NRG 评分与治疗药物 Log IC50 值之间的统计度量 Spearman 秩相关系数。随后，我们根据模型评分将 TCGA-AML 队列分为两组，一组为高评分组，另一组为低评分组。与低 NRG 评分组相比，NRG 评分高的 AML 患者的估计总生存率（OS）率较低，这在验证组中得到了证实。构建的 NRG 特征对 AML 的预后价值，在单变量和多变量逐步回归分析中均得到了验证，与其他变量独立。当比较来自 2 个组的与免疫系统相关的专门细胞的浸润状态时，B 细胞幼稚、浆细胞和单核细胞在各种样本亚群之间存在显著差异。此外，与坏死特征相关的 30 个标志性通路在高/低 NRG 评分组之间存在显著差异。并且在骨髓淋巴细胞、分类和 FAB 分类的临床特征中，患者表现出显著的 NRG 评分分布。此外，我们发现 BIRB0796、VX680、Vorinostat 和 Axitinib 与 NRG 评分呈正相关，而 CI.1040、PD.0325901、Z.L LNle.CHO 和 AZD6244 与 NRG 评分呈负相关。这些药物可能为后续治疗提供参考。
