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High Expression of DC-STAMP Gene Predicts Adverse Outcomes in AML

Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy with poor prognosis. We explored the RNA sequence data and clinical information of AML patients from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database to search for the core molecule for...

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Autores principales: Liang, Qian, Zhang, Lele, Wang, Wenjun, Zhao, Jingyu, Li, Qiaoli, Pan, Hong, Gao, Zhen, Fang, Liwei, Shi, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091727/
https://www.ncbi.nlm.nih.gov/pubmed/35571050
http://dx.doi.org/10.3389/fgene.2022.876689
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author Liang, Qian
Zhang, Lele
Wang, Wenjun
Zhao, Jingyu
Li, Qiaoli
Pan, Hong
Gao, Zhen
Fang, Liwei
Shi, Jun
author_facet Liang, Qian
Zhang, Lele
Wang, Wenjun
Zhao, Jingyu
Li, Qiaoli
Pan, Hong
Gao, Zhen
Fang, Liwei
Shi, Jun
author_sort Liang, Qian
collection PubMed
description Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy with poor prognosis. We explored the RNA sequence data and clinical information of AML patients from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database to search for the core molecule for prognosis. The DC-STAMP expression was significantly higher in AML patients, which was linked to old age, unfavorable cytogenetic risk, and death (all p < 0.05). Furthermore, it was revealed that high DC-STAMP expression was an independent unfavorable factor for overall survival (OS) by univariate analysis [hazard ratio (HR): 2.683; 95% confidence interval (CI): 1.723–4.178; p < 0.001] and multivariate analysis (HR: 1.733; 95% CI: 1.079–2.781; p = 0.023). The concordance index (C-index 0.734, 95% CI: 0.706–0.762), calibration curves, and decision curve analysis showed the certain predictive accuracy of a nomogram model based on multivariate analysis for OS. In addition, we found that the differentially expressed gene (DEG) enrichment pathways of high- and low-DC-STAMP expression group enrichment pathways were focused on channel activity and platelet alpha granule by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), while gene set enrichment analysis (GSEA) pathways were mainly involved in mTORC1 signaling and TNF-α signaling via the NF-kB pathway. Moreover, a protein–protein interaction (PPI) network demonstrated that DC-STAMP interacted with two hub genes (PPBP and PF4), which were highly regulated and associated with poor survival. Finally, high DC-STAMP expression showed a significantly positive correlation with four immune cell [NK CD56 (dim) cells, macrophages, cytotoxic cells, and CD8 (+) T cells] infiltration and high level of immune checkpoint genes (PDCD1, CD274, CTLA-4, and TIGIT). Therefore, our results suggest that high expression of DC-STAMP predicts adverse outcomes for AML patients.
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spelling pubmed-90917272022-05-12 High Expression of DC-STAMP Gene Predicts Adverse Outcomes in AML Liang, Qian Zhang, Lele Wang, Wenjun Zhao, Jingyu Li, Qiaoli Pan, Hong Gao, Zhen Fang, Liwei Shi, Jun Front Genet Genetics Acute myeloid leukemia (AML) is a genetically heterogeneous hematological malignancy with poor prognosis. We explored the RNA sequence data and clinical information of AML patients from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database to search for the core molecule for prognosis. The DC-STAMP expression was significantly higher in AML patients, which was linked to old age, unfavorable cytogenetic risk, and death (all p < 0.05). Furthermore, it was revealed that high DC-STAMP expression was an independent unfavorable factor for overall survival (OS) by univariate analysis [hazard ratio (HR): 2.683; 95% confidence interval (CI): 1.723–4.178; p < 0.001] and multivariate analysis (HR: 1.733; 95% CI: 1.079–2.781; p = 0.023). The concordance index (C-index 0.734, 95% CI: 0.706–0.762), calibration curves, and decision curve analysis showed the certain predictive accuracy of a nomogram model based on multivariate analysis for OS. In addition, we found that the differentially expressed gene (DEG) enrichment pathways of high- and low-DC-STAMP expression group enrichment pathways were focused on channel activity and platelet alpha granule by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), while gene set enrichment analysis (GSEA) pathways were mainly involved in mTORC1 signaling and TNF-α signaling via the NF-kB pathway. Moreover, a protein–protein interaction (PPI) network demonstrated that DC-STAMP interacted with two hub genes (PPBP and PF4), which were highly regulated and associated with poor survival. Finally, high DC-STAMP expression showed a significantly positive correlation with four immune cell [NK CD56 (dim) cells, macrophages, cytotoxic cells, and CD8 (+) T cells] infiltration and high level of immune checkpoint genes (PDCD1, CD274, CTLA-4, and TIGIT). Therefore, our results suggest that high expression of DC-STAMP predicts adverse outcomes for AML patients. Frontiers Media S.A. 2022-04-27 /pmc/articles/PMC9091727/ /pubmed/35571050 http://dx.doi.org/10.3389/fgene.2022.876689 Text en Copyright © 2022 Liang, Zhang, Wang, Zhao, Li, Pan, Gao, Fang and Shi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Liang, Qian
Zhang, Lele
Wang, Wenjun
Zhao, Jingyu
Li, Qiaoli
Pan, Hong
Gao, Zhen
Fang, Liwei
Shi, Jun
High Expression of DC-STAMP Gene Predicts Adverse Outcomes in AML
title High Expression of DC-STAMP Gene Predicts Adverse Outcomes in AML
title_full High Expression of DC-STAMP Gene Predicts Adverse Outcomes in AML
title_fullStr High Expression of DC-STAMP Gene Predicts Adverse Outcomes in AML
title_full_unstemmed High Expression of DC-STAMP Gene Predicts Adverse Outcomes in AML
title_short High Expression of DC-STAMP Gene Predicts Adverse Outcomes in AML
title_sort high expression of dc-stamp gene predicts adverse outcomes in aml
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091727/
https://www.ncbi.nlm.nih.gov/pubmed/35571050
http://dx.doi.org/10.3389/fgene.2022.876689
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