Integrated analysis reveals distinct molecular, clinical, and immunological features of B7-H3 in acute myeloid leukemia.
B7-H3
acute myeloid leukemia
immune checkpoint
prognosis
Journal
Cancer medicine
ISSN: 2045-7634
Titre abrégé: Cancer Med
Pays: United States
ID NLM: 101595310
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
25
06
2021
received:
09
01
2021
accepted:
29
08
2021
pubmed:
26
9
2021
medline:
18
3
2022
entrez:
25
9
2021
Statut:
ppublish
Résumé
The role of B7-H3 in acute myeloid leukemia (AML) is not fully understood. Two previous studies investigating its expression and significances in AML are partially different. In this study, we aimed to systematically characterize the genomic and immune landscape in AML patients with altered B7-H3 expression using multi-omics data in the public domain. We found significantly increased B7-H3 expression in AML compared to either other hematological malignancies or healthy controls. Clinically, high B7-H3 expression was associated with old age, TP53 mutations, wild-type WT1 and CEBPA, and the M3 and M5 FAB subtypes. Moreover, we observed that increased B7-H3 expression correlated significantly with a poor outcome of AML patients in four independent datasets. Gene set enrichment analysis (GSEA) revealed the enrichment of the "EMT" oncogenic gene signatures in high B7-H3 expressers. Further investigation suggested that B7-H3 was more likely to be associated with immune-suppressive cells (macrophages, neutrophils, dendritic cells, and Th17 cells). B7-H3 was also positively associated with a number of checkpoint genes, such as VISTA (B7-H5), CD80 (B7-1), CD86 (B7-2), and CD70. In summary, we uncovered distinct genomic and immunologic features associated with B7-H3 expression in AML. This may lead to a better understanding of the molecular mechanisms underlying B7-H3 dysregulation in AML and to the development of novel therapeutic strategies.
Identifiants
pubmed: 34562306
doi: 10.1002/cam4.4284
pmc: PMC8559480
doi:
Substances chimiques
B7 Antigens
0
CD276 protein, human
0
Immune Checkpoint Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7831-7846Subventions
Organisme : "Liu Ge Yi Gong Cheng" of Jiangsu Province
ID : LGY2018024
Organisme : youth medical talents project of "Ke Jiao Qiang Wei" project of Jiangsu province
ID : QNRC2016450
Organisme : Social Development Foundation of Zhenjiang
ID : SH2019065
Organisme : National Natural Science Foundation of China
ID : 81970118
Organisme : National Natural Science Foundation of China
ID : 81900163
Organisme : Scientific Research Project of The Fifth 169 Project of Zhenjiang
ID : 21
Organisme : Zhenjiang Clinical Research Center of Hematology
ID : SS2018009
Organisme : Medical Innovation Team of Jiangsu Province
ID : CXTDB2017002
Informations de copyright
© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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