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A Novel Identified Necroptosis-Related Risk Signature for Prognosis Prediction and Immune Infiltration Indication in Acute Myeloid Leukemia Patients

AML ranks second in the most common types of leukemia diagnosed in both adults and children. Necroptosis is a programmed inflammatory cell death form reported to be an innate immune effector against microbial and viral pathogens and recently has been found to play an eventful role in the oncogenesis...

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Autores principales: Sun, Yong, Wang, Ruiheng, Xie, Shufeng, Wang, Yuanli, Liu, Han
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602382/
https://www.ncbi.nlm.nih.gov/pubmed/36292722
http://dx.doi.org/10.3390/genes13101837
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author Sun, Yong
Wang, Ruiheng
Xie, Shufeng
Wang, Yuanli
Liu, Han
author_facet Sun, Yong
Wang, Ruiheng
Xie, Shufeng
Wang, Yuanli
Liu, Han
author_sort Sun, Yong
collection PubMed
description AML ranks second in the most common types of leukemia diagnosed in both adults and children. Necroptosis is a programmed inflammatory cell death form reported to be an innate immune effector against microbial and viral pathogens and recently has been found to play an eventful role in the oncogenesis, progression, and metastasis of cancer. This study is designed to explore the potential value of necroptosis in predicting prognostic and optimizing the current therapeutic strategies for AML patients. We collected transcriptome and clinical data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases and selected necroptosis-related genes with both differential significance and prognostic value. Six genes (YBX3, ZBP1, CDC37, ALK, BRAF, and BNIP3) were incorporated to generate a risk model with the implementation of multivariate Cox regression. The signature was proven to be an independent prognostic predictor in both training and validation cohorts with hazard ratios (HRs) of 1.51 (95% CI: 1.33–1.72) and 1.57 (95% CI: 1.16–2.12), respectively. Moreover, receiver operating characteristic (ROC) curve was utilized to quantify the predictive performance of the signature and satisfying results were shown with the area under the curve (AUC) up to 0.801 (3-year) and 0.619 (3-year), respectively. In addition, the subtyping of AML patients based on the risk signature demonstrated a significant correlation with the immune cell infiltration and response to immunotherapy. Finally, we incorporated risk signature with the classical clinical features to establish a nomogram which may contribute to the improvement of clinical management. To conclude, this study identified a necroptosis-related signature as a novel biomarker to improve the risk stratification, to inform the immunotherapy efficacy, and to indicate the therapeutic option of targeted therapy.
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spelling pubmed-96023822022-10-27 A Novel Identified Necroptosis-Related Risk Signature for Prognosis Prediction and Immune Infiltration Indication in Acute Myeloid Leukemia Patients Sun, Yong Wang, Ruiheng Xie, Shufeng Wang, Yuanli Liu, Han Genes (Basel) Article AML ranks second in the most common types of leukemia diagnosed in both adults and children. Necroptosis is a programmed inflammatory cell death form reported to be an innate immune effector against microbial and viral pathogens and recently has been found to play an eventful role in the oncogenesis, progression, and metastasis of cancer. This study is designed to explore the potential value of necroptosis in predicting prognostic and optimizing the current therapeutic strategies for AML patients. We collected transcriptome and clinical data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases and selected necroptosis-related genes with both differential significance and prognostic value. Six genes (YBX3, ZBP1, CDC37, ALK, BRAF, and BNIP3) were incorporated to generate a risk model with the implementation of multivariate Cox regression. The signature was proven to be an independent prognostic predictor in both training and validation cohorts with hazard ratios (HRs) of 1.51 (95% CI: 1.33–1.72) and 1.57 (95% CI: 1.16–2.12), respectively. Moreover, receiver operating characteristic (ROC) curve was utilized to quantify the predictive performance of the signature and satisfying results were shown with the area under the curve (AUC) up to 0.801 (3-year) and 0.619 (3-year), respectively. In addition, the subtyping of AML patients based on the risk signature demonstrated a significant correlation with the immune cell infiltration and response to immunotherapy. Finally, we incorporated risk signature with the classical clinical features to establish a nomogram which may contribute to the improvement of clinical management. To conclude, this study identified a necroptosis-related signature as a novel biomarker to improve the risk stratification, to inform the immunotherapy efficacy, and to indicate the therapeutic option of targeted therapy. MDPI 2022-10-11 /pmc/articles/PMC9602382/ /pubmed/36292722 http://dx.doi.org/10.3390/genes13101837 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sun, Yong
Wang, Ruiheng
Xie, Shufeng
Wang, Yuanli
Liu, Han
A Novel Identified Necroptosis-Related Risk Signature for Prognosis Prediction and Immune Infiltration Indication in Acute Myeloid Leukemia Patients
title A Novel Identified Necroptosis-Related Risk Signature for Prognosis Prediction and Immune Infiltration Indication in Acute Myeloid Leukemia Patients
title_full A Novel Identified Necroptosis-Related Risk Signature for Prognosis Prediction and Immune Infiltration Indication in Acute Myeloid Leukemia Patients
title_fullStr A Novel Identified Necroptosis-Related Risk Signature for Prognosis Prediction and Immune Infiltration Indication in Acute Myeloid Leukemia Patients
title_full_unstemmed A Novel Identified Necroptosis-Related Risk Signature for Prognosis Prediction and Immune Infiltration Indication in Acute Myeloid Leukemia Patients
title_short A Novel Identified Necroptosis-Related Risk Signature for Prognosis Prediction and Immune Infiltration Indication in Acute Myeloid Leukemia Patients
title_sort novel identified necroptosis-related risk signature for prognosis prediction and immune infiltration indication in acute myeloid leukemia patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9602382/
https://www.ncbi.nlm.nih.gov/pubmed/36292722
http://dx.doi.org/10.3390/genes13101837
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