背景:探索预测临床结果的潜在生物标志物和开发急性髓细胞性白血病(AML)的靶向治疗是至关重要的。本研究旨在探讨硫氧还蛋白相互作用蛋白(TXNIP)/核苷酸结合寡聚化结构域(NOD)样受体蛋白3(NLRP3)通路的表达模式及其在AML患者预后中的作用。方法:在本研究中,我们使用来自基因表达综合(GEO)的微阵列数据和来自癌症基因组图谱(TCGA)的转录组数据检测了TXNIP/NLRP3通路在AML患者中的预后价值,以建立预后模型,并通过定量实时PCR(qRT-PCR)在来自暨南大学(JNU)数据库的26例AML患者和18例健康个体的验证队列中验证了结果.结果:对GSE13159数据库的分析显示,TXNIP,在AML患者中,TXNIP/NLRP3通路内的白细胞介素1β(IL1B)显著上调,caspase1(CASP1)下调(TXNIP,P=0.031;IL1B,P=0.042;CASP1,P=0.038)。与高NLRP3表达相比,在GSE12417数据集中,具有低NLRP3表达的AML患者具有更长的总生存期(OS)(P=0.004)。此外,训练和验证结果表明,TXNIP较低,NLRP3和IL1B表达与良好预后相关(GSE12417,P=0.009;TCGA,P=0.050;JNU,P=0.026)。根据接收机工作特性曲线分析,该模型对预测3年生存率的敏感性为84%.这些数据可能为AML结果提供新的预测因子,并为进一步研究在AML的新靶向治疗中使用TXNIP/NLRP3/IL1B基因的可能性提供指导。
Background: Exploring potential biomarkers for predicting clinical outcomes and developing targeted therapies for acute myeloid leukemia (AML) is of utmost importance. This study aimed to investigate the expression pattern of the thioredoxin-interacting protein (TXNIP)/nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) pathway and its role in the prognosis of AML patients. Methods: In this study, we examined the prognostic value of TXNIP/NLRP3 pathway in AML patients using microarray data from Gene Expression Omnibus (GEO) and transcriptome data from the Cancer Genome Atlas (TCGA) to develop a prognostic model and validated the results by quantitative real-time PCR (qRT-PCR) in a validation cohort of 26 AML patients and 18 healthy individuals from Jinan University (JNU) database. Results: Analysis of the GSE13159 database revealed that TXNIP, interleukin 1 beta (IL1B) within the TXNIP/NLRP3 pathway were significantly upregulated and caspase1 (CASP1) was downregulated in AML patients (TXNIP, P = 0.031; IL1B, P = 0.042; CASP1, P = 0.038). Compared to high NLRP3 expression, AML patients with low NLRP3 expression had a longer overall survival (OS) in the GSE12417 dataset (P = 0.004). Moreover, both the training and validation results indicated that lower TXNIP, NLRP3, and IL1B expression were associated with favorable prognosis (GSE12417, P = 0.009; TCGA, P = 0.050; JNU, P = 0.026). According to the receiver operating characteristic curve analysis, this model demonstrated a sensitivity of 84% for predicting three-year survival. These data might provide novel predictors for AML outcome and direction for further investigation of the possibility of using TXNIP/NLRP3/IL1B genes in novel targeted therapies for AML.