Liu Songyang, Luo Dongmei, Luo Jie, Liang Hanyin, Zhi Yunfei, Wang Dong, Xu Na
The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China.
Int J Gen Med. 2022 Mar 12;15:2913-2927. doi: 10.2147/IJGM.S352062. eCollection 2022.
Acute myelogenous leukemia (AML) is a common and fatal disease in hematology with frequent relapses and a poor prognosis. Pyroptosis, a programmed cell death mediated by inflammasomes, has been shown to be associated with leukemia recently. However, the role of pyroptosis for diagnosis and prognosis in AML remained less understood.
We downloaded three public datasets and constructed a signature of TCGA cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model to predict the overall survival of AML patients. Samples from the GEO database were treated as a validation cohort. Gone through LASSO-Cox regression analysis, an 8-PRG-related signature was developed. Used the median score from the signature, we classified patients in two subgroups. Subsequently, we employed univariate COX, multivariate Cox regression, ROC analysis and constructed a nomogram, Finally, differential analysis, GO and KEGG functional analysis, ESTIMATE algorithm and CIBERSORT algorithm were used to explore the difference between two groups.
The expression levels of 90.9% pyroptosis-related genes (PRGs) had significant difference compared AML with normal tissues. The results of univariate COX regression analysis demonstrated 10 differentially expressed genes (DEGs) were associated with patients' OS (p < 0.05). Then, we found OS of patients in the low-risk group was more likely to be lengthened compared with their high-risk counterparts (P < 0.05 both in the TCGA and GEO cohort). After controlling clinical factors, the risk score could still remain an independent predictive element (HR > 1, P < 0.001) of OS in multivariate Cox regression analysis. Furthermore, a nomogram with prognostic value for AML was thus established. Time-dependent ROC analysis proved the predictive power of the signature. Functional analysis suggested that DEGs were mainly concentrated in immune-related pathways, such as humoral immune response and T cell proliferation. TME scores and risk scores were strongly correlated and immune status differed between the risk subgroups.
A novel PRG-related signature was established to forecast the prognosis in AML, and pyroptosis may be a potential therapeutic target for AML.
急性髓系白血病（AML）是血液学中一种常见的致命疾病，复发频繁且预后较差。细胞焦亡是一种由炎性小体介导的程序性细胞死亡，最近已被证明与白血病有关。然而，细胞焦亡在AML诊断和预后中的作用仍知之甚少。
我们下载了三个公共数据集，并使用最小绝对收缩和选择算子（LASSO）Cox回归模型构建了TCGA队列的特征，以预测AML患者的总生存期。来自GEO数据库的样本被视为验证队列。通过LASSO-Cox回归分析，开发了一个与8个焦亡相关基因（PRG）的特征。利用该特征的中位数评分，我们将患者分为两个亚组。随后，我们采用单因素COX、多因素Cox回归、ROC分析并构建了列线图。最后，使用差异分析、GO和KEGG功能分析、ESTIMATE算法和CIBERSORT算法来探索两组之间的差异。
与正常组织相比，90.9%的细胞焦亡相关基因（PRG）在AML中的表达水平有显著差异。单因素Cox回归分析结果显示，10个差异表达基因（DEG）与患者的总生存期相关（p < 0.05）。然后，我们发现低风险组患者的总生存期比高风险组患者更有可能延长（在TCGA和GEO队列中均P < 0.05）。在控制临床因素后，风险评分在多因素Cox回归分析中仍可作为总生存期（HR > 1，P < 0.001）的独立预测因素。此外，由此建立了一个对AML具有预后价值的列线图。时间依赖性ROC分析证明了该特征的预测能力。功能分析表明，差异表达基因主要集中在免疫相关途径，如体液免疫反应和T细胞增殖。肿瘤微环境（TME）评分与风险评分高度相关，且风险亚组之间的免疫状态不同。
建立了一种新的与PRG相关的特征来预测AML的预后，细胞焦亡可能是AML的一个潜在治疗靶点。
