Analysis of prognostic biomarker models of TXNIP/NLRP3/IL1B inflammasome pathway in patients with acute myeloid leukemia
Junjie Chen, Qi Hou, Tao Chang, Jiamian Zheng, Chao Yao, Junyi He, Shengting Chen, Xiuli Wu, Zhenyi Jin
Abstract
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.