Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, P.R. China.
Zhenjiang Clinical Research Center of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, P.R. China.
Aging (Albany NY). 2023 Nov 21;15(24):14677-14702. doi: 10.18632/aging.205231.
Necroptosis is a tightly regulated form of necrotic cell death that promotes inflammation and contributes to disease development. However, the potential roles of necroptosis-related genes (NRGs) in acute myeloid leukemia (AML) have not been elucidated fully.
We conducted a study to identify a robust biomarker signature for predicting the prognosis and immunotherapy efficacy based on NRGs in AML. We analyzed the genetic and transcriptional alterations of NRGs in 151 patients with AML. Then, we identified three necroptosis clusters. Moreover, a necroptosis score was constructed and assessed based on the differentially expressed genes (DEGs) between the three necroptosis clusters.
Three necroptosis clusters were correlated with clinical characteristics, prognosis, the tumor microenvironment, and infiltration of immune cells. A high necroptosis score was positively associated with a poor prognosis, immune-cell infiltration, expression of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1), immune score, stromal score, interferon-gamma (IFNG), merck18, T-cell dysfunction-score signatures, and cluster of differentiation-86, but negatively correlated with tumor immune dysfunction and exclusion score, myeloid-derived suppressor cells, and M2-type tumor-associated macrophages. Our observations indicated that a high necroptosis score might contribute to immune evasion. More interestingly, AML patients with a high necroptosis score may benefit from treatment based on immune checkpoint blockade.
Consequently, our findings may contribute to deeper understanding of NRGs in AML, and facilitate assessment of the prognosis and treatment strategies.
细胞坏死性凋亡是一种受严格调控的细胞坏死形式，可促进炎症反应，并有助于疾病的发展。然而，细胞坏死性凋亡相关基因（NRGs）在急性髓系白血病（AML）中的潜在作用尚未完全阐明。
我们进行了一项研究，旨在基于 AML 中的 NRGs 确定用于预测预后和免疫疗法疗效的稳健生物标志物特征。我们分析了 151 例 AML 患者的 NRGs 的遗传和转录改变。然后，我们鉴定了三个坏死性凋亡簇。此外，基于三个坏死性凋亡簇之间的差异表达基因（DEGs）构建并评估了坏死性凋亡评分。
三个坏死性凋亡簇与临床特征、预后、肿瘤微环境和免疫细胞浸润相关。高坏死性凋亡评分与预后不良、免疫细胞浸润、程序性细胞死亡 1/程序性细胞死亡配体 1（PD-1/PD-L1）表达、免疫评分、基质评分、干扰素-γ（IFNG）、merck18、T 细胞功能障碍评分特征和分化群-86呈正相关，但与肿瘤免疫功能障碍和排斥评分、髓样来源抑制细胞和 M2 型肿瘤相关巨噬细胞呈负相关。我们的观察结果表明，高坏死性凋亡评分可能有助于免疫逃逸。更有趣的是，高坏死性凋亡评分的 AML 患者可能受益于基于免疫检查点阻断的治疗。
因此，我们的研究结果可能有助于深入了解 AML 中的 NRGs，并促进预后评估和治疗策略。
