Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Genes (Basel). 2022 Dec 3;13(12):2281. doi: 10.3390/genes13122281.
Pyroptosis is an inflammatory form of programmed necrotic cell death, but its potential prognostic value in acute myeloid leukemia (AML) remains unclear. On the basis of available AML data from TCGA and TARGET databases, a 10-gene signature model was constructed to effectively predict AML prognosis by performing LASSO Cox regression analysis, which showed that patients with a low-risk score had a significantly better prognosis than that of the high-risk group, and receiver operator characteristic (ROC) analysis achieved superior performance in the prognostic model. The model was further well-verified in an external GEO cohort. Multivariable Cox regression analysis showed that, in addition to age, the risk score was an independent poor survival factor for AML patients, and a nomogram model was constructed with high accuracy. Moreover, the high-risk group generally had higher cytolytic activity and increased levels of infiltrating immune cells, including tumor-infiltrating lymphocytes (TILs) and regulatory T cells (Tregs), which could be related to the expression of immune checkpoint genes. Additionally, low-risk AML patients may have a better response from traditional chemotherapeutic drugs. In conclusion, a pyroptosis-related gene signature can independently predict the prognosis of AML patients with sufficient predictive power, and pyroptosis plays an important role in the immune microenvironment of AML, which may be used to develop a new effective therapeutic method for AML in the future.
细胞焦亡是一种炎性形式的程序性细胞坏死，但它在急性髓系白血病（AML）中的潜在预后价值尚不清楚。基于 TCGA 和 TARGET 数据库中现有的 AML 数据，通过 LASSO Cox 回归分析构建了一个 10 基因签名模型，有效地预测了 AML 的预后，结果表明低风险评分的患者的预后明显好于高风险组，且在预后模型中，接收者操作特征（ROC）分析的表现也很出色。该模型在另一个外部 GEO 队列中也得到了很好的验证。多变量 Cox 回归分析表明，除年龄外，风险评分是 AML 患者不良生存的独立预后因素，且构建了具有高准确性的列线图模型。此外，高风险组通常具有更高的细胞溶解活性和浸润免疫细胞水平的增加，包括肿瘤浸润淋巴细胞（TILs）和调节性 T 细胞（Tregs），这可能与免疫检查点基因的表达有关。此外，低危 AML 患者可能对传统化疗药物有更好的反应。总之，一个与细胞焦亡相关的基因特征可以独立预测 AML 患者的预后，并且具有足够的预测能力，细胞焦亡在 AML 的免疫微环境中起着重要作用，这可能在未来用于开发 AML 的新的有效治疗方法。
