An immunity and pyroptosis gene-pair signature predicts overall survival in acute myeloid leukemia

Abstract

Treatment responses of patients with acute myeloid leukemia (AML) are known to be heterogeneous, posing challenges for risk scoring and treatment stratification. In this retrospective multi-cohort study, we investigated whether combining pyroptosis- and immune-related genes improves prognostic classification of AML patients. Using a robust gene pairing approach, which effectively eliminates batch effects across heterogeneous patient cohorts and transcriptomic data, we developed an immunity and pyroptosis-related prognostic (IPRP) signature that consists of 15 genes. Using 5 AML cohorts (n = 1327 patients total), we demonstrate that the IPRP score leads to more consistent and accurate survival prediction performance, compared with 10 existing signatures, and that IPRP scoring is widely applicable to various patient cohorts, treatment procedures and transcriptomic technologies. Compared to current standards for AML patient stratification, such as age or ELN2017 risk classification, we demonstrate an added prognostic value of the IPRP risk score for providing improved prediction of AML patients. Our web-tool implementation of the IPRP score and a simple 4-factor nomogram enables practical and robust risk scoring for AML patients. Even though developed for AML patients, our pan-cancer analyses demonstrate a wider application of the IPRP signature for prognostic prediction and analysis of tumor-immune interplay also in multiple solid tumors.

Development of a novel pyroptosis-related LncRNA signature with multiple significance in acute myeloid leukemia

“…Besides risk score, molecular risk and age were shown to be independent risk factors for OS and then were enrolled to multivariate Cox regression ( Figure 5A ). The risk score demonstrated a higher predictive ability than that of clinicopathological variables in AML ( Figure 5B ) and other previously reported prognostic signatures [Leu 2022 ( Kong et al, 2022 ), AJH 2021 ( Chen et al, 2021 ), Int Imp 2022 ( Shao et al, 2022 )] (iAUC-Our signature: 0.806, iAUC-Leu2022: 0.691, iAUC-AJH2021: 0.570, and iAUC-IntImp2022: 0.658; all the p -values in comparisons between Our signature and the above three models were <0.001). Based on multivariate Cox regression, we developed a novel nomogram, aiming to optimize the predictive accuracy of the risk model ( Figure 5D ).…”

“…Irreversible pyroptotic cell death may be caused by the activation of inflammasome in HSCs and thus leading to the origin of hematopoietic malignancies ( Wei et al, 2022 ). An immunity and pyroptosis gene-pair signature performed stronger survival predictive efficacy than 10 existing signatures ( Kong et al, 2022 ). The researches for the relationship between pyroptosis and tumor may provide some inspirations for clinical treatments.…”

Correlations between the modification patterns mediated by pyroptosis-related genes, tumor microenvironment, and immunotherapy in soft tissue sarcoma

“…Based on previous studies, we identified 52 PRGs. [25][26][27] Wilcox tests were used to assess the expression differences of PRGs between normal soft tissue and STS, and P < .05 was used as the screening criterion. Using the package "ConsensusClusterPlus," we carried out the cluster analysis based on 52 PRGs expressions in STS patients.…”

Pyroptosis and Its Role in Cervical Cancer

“…Pyroptosis is mainly mediated by inflammasomes and the activation of caspase family members including caspase-1, which leads to splicing and polymerization of multifarious Gasdermin family members such as GSDMD, contributing to cell perforation and then cell death [ 32 ]. Its activation mechanisms mainly include canonical, noncanonical inflammasome pathways and others.…”