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. 2024 May 27;21(8):1438-1446.
doi: 10.7150/ijms.96627. eCollection 2024.

Analysis of prognostic biomarker models of TXNIP/NLRP3/IL1B inflammasome pathway in patients with acute myeloid leukemia

Junjie Chen  1 , Qi Hou  1 , Tao Chang  2 , Jiamian Zheng  1   3 , Chao Yao  1 , Junyi He  1 , Shengting Chen  4 , Xiuli Wu  1   3 , Zhenyi Jin  3   5
Affiliations

Analysis of prognostic biomarker models of TXNIP/NLRP3/IL1B inflammasome pathway in patients with acute myeloid leukemia

Junjie Chen et al. Int J Med Sci. .

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.

Keywords: Acute myeloid leukemia; NLRP3; TXNIP; biomarker; prognosis.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Relative expression and OS analysis of TXNIP, NLRP3, CASP1, and IL1B in GSE13159 and GSE12417. (A) Relative expression of TXNIP, NLRP3, CASP1 and IL1B in AML patients and HIs. (B) OS analysis of high and low expression of TXNIP, NLRP3, CASP1, IL1B in GSE12417 dataset, Kaplan-Meier curves were plotted.
Figure 2
Figure 2
Co-expression patterns of TXNIP, NLRP3, CASP1, and IL1B in AML patients in GSE12417 dataset. (A) OS analysis of TXNIPlowNLRP3low, TXNIPlowCASP1low, TXNIPlowIL1Blow, and (B)TXNIPlowNLRP3lowCASP1low, (C) TXNIPlowNLRP3lowIL1Blow (left panel). The analysis of RMST, 3-year RMST was plotted (right panel).
Figure 3
Figure 3
Co-expression patterns of TXNIP, NLRP3, CASP1, and IL1B in AML patients in TCGA database. (A) OS analysis of TXNIPlowNLRP3low, TXNIPlowCASP1low, TXNIPlowIL1Blow, and (B) TXNIPlowNLRP3lowCASP1low, (C) TXNIPlowNLRP3lowIL1Blow (left panel). The analysis of RMST, 3-year RMST was plotted (right panel).
Figure 4
Figure 4
Validation results of JNU dataset (A) Relative expression of TXNIP, NLRP3, CASP1 and IL1B in AML patients and HIs. (B) Single expression patterns of TXNIP, NLRP3, CASP1, and IL1B were plotted to be forest plot. (C) Low co-expression TXNIP/NLRP3 AML patients had a better OS. (D) and (E) triple expression patterns of TXNIP, NLRP3, CASP1, IL1B and AUC of TXNIP/NLRP3/IL1B (right panel).
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