Research Paper|Volume 15, Issue 24|pp 14677—14702

Identification and validation of necroptosis-related gene signatures to predict clinical outcomes and therapeutic responses in acute myeloid leukemia

Xiang-Mei Wen^1,^2,³, Zi-Jun Xu^1,^2,³, Ji-Chun Ma^1,^2,³, Pei-Hui Xia^1,^2,³, Ye Jin^2,⁴, Xin-Yi Chen^1,^2,³, Wei Qian⁵, Jiang Lin^1,^2,³, Jun Qian^2,⁴

¹Laboratory Center, Affiliated People’s Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, P.R. China
²Zhenjiang Clinical Research Center of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, P.R. China
³The Key Lab of Precision Diagnosis and Treatment in Hematologic Malignancies of Zhenjiang City, Affiliated People’s Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, P.R. China
⁴Department of Hematology, Affiliated People’s Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, P.R. China
⁵Department of Otolaryngology-Head and Neck Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang 212002, Jiangsu, P.R. China

* Equal contribution

Received: May 15, 2023Accepted: October 2, 2023Published: November 21, 2023

https://doi.org/10.18632/aging.205231

Copyright: © 2023 Wen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Necroptosis is a tightly regulated form of necrotic cell death that promotes inflammation and contributes to disease development. However, the potential roles of necroptosis-related genes (NRGs) in acute myeloid leukemia (AML) have not been elucidated fully.

Methods: We conducted a study to identify a robust biomarker signature for predicting the prognosis and immunotherapy efficacy based on NRGs in AML. We analyzed the genetic and transcriptional alterations of NRGs in 151 patients with AML. Then, we identified three necroptosis clusters. Moreover, a necroptosis score was constructed and assessed based on the differentially expressed genes (DEGs) between the three necroptosis clusters.

Results: Three necroptosis clusters were correlated with clinical characteristics, prognosis, the tumor microenvironment, and infiltration of immune cells. A high necroptosis score was positively associated with a poor prognosis, immune-cell infiltration, expression of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1), immune score, stromal score, interferon-gamma (IFNG), merck18, T-cell dysfunction-score signatures, and cluster of differentiation-86, but negatively correlated with tumor immune dysfunction and exclusion score, myeloid-derived suppressor cells, and M2-type tumor-associated macrophages. Our observations indicated that a high necroptosis score might contribute to immune evasion. More interestingly, AML patients with a high necroptosis score may benefit from treatment based on immune checkpoint blockade.

Conclusions: Consequently, our findings may contribute to deeper understanding of NRGs in AML, and facilitate assessment of the prognosis and treatment strategies.