PMID- 38482057
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240315
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 15
DP  - 2024
TI  - A hypoxia-related genes prognostic risk model, and mechanisms of hypoxia 
      contributing to poor prognosis through immune microenvironment and drug 
      resistance in acute myeloid leukemia.
PG  - 1339465
LID - 10.3389/fphar.2024.1339465 [doi]
LID - 1339465
AB  - Objective: Acute myeloid leukemia (AML) is a malignant hematologic cancer with 
      poor prognosis. Emerging evidence suggests a close association between AML 
      progression and hypoxia. The purpose of this study was to establish a new risk 
      prognostic model for AML based on hypoxia-related genes, and to explore the 
      mechanisms by which hypoxia-related genes affect the prognosis of AML based on 
      tumor immune microenvironment (TIME) and drug resistance. Methods: The AML 
      patient samples obtained from Therapeutically Applicable Research to Generate 
      Effective Treatments (TARGET) database were classified into C1 and C2 based on 
      hypoxia-related genes, followed by analysis utilizing Gene Ontology (GO), Kyoto 
      Encyclopaedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis 
      (GSEA). Through univariate and LASSO Cox regression analysis, the hypoxia-related 
      hub genes 26S proteasome non-ATPase regulatory subunit 11 (PSMD11) and 26S 
      proteasome non-ATPase regulatory subunit 14 (PSMD14) were identified to construct 
      the model. AML patient samples were obtained from the TARGET and The Cancer 
      Genome Atlas (TCGA) databases, serving as the training and the validation sets, 
      and were stratified into high-risk and low-risk group according to the median 
      risk score. The correlations between the model and TIME and anti-tumor drugs were 
      analysed using CIBERSORT and Genomics of Drug Sensitivity in Cancer (GDSC) 
      databases. The expressions of PSMD11/PSMD14 in clinical samples and AML sensitive 
      and drug-resistant cell lines were detected by Western blot and real-time PCR. 
      Results: The C1 group with high expression of hypoxia-related genes had lower 
      overall survival (OS). Immune-related signaling pathways were different between 
      C1/C2, and hypoxia was positively correlated with the activation of mammalian 
      target of rapamycin (mTOR) signaling pathway. The model had good accuracy in both 
      the training and the validation sets. The high-risk group exhibited lower OS and 
      TIME activity, and was more sensitive to several anti-tumor drugs. PSMD11/PSMD14 
      were highly expressed in relapsed patients and AML drug-resistant cell lines. 
      Conclusion: The established novel risk prognostic model and experiment results 
      offer valuable insights for predicting AML prognosis and guiding drug selection. 
      It also provides a fundamental framework for the mechanisms through which hypoxia 
      impacts AML prognosis by modulating TIME and drug resistance.
CI  - Copyright (c) 2024 Liu, Wang, Kang, Feng and Wang.
FAU - Liu, Xin
AU  - Liu X
AD  - Clinical Medical College, Guizhou Medical University, Guiyang, Guizhou, China.
FAU - Wang, Li
AU  - Wang L
AD  - School of Basic Medical, Guizhou Medical University, Guiyang, Guizhou, China.
FAU - Kang, Qian
AU  - Kang Q
AD  - Department of Hematology, Affiliated Hospital of Guizhou Medical University, 
      Guizhou Province Institute of Hematology, Guizhou Province Laboratory of 
      Hematopoietic Stem Cell Transplantation Centre, Guiyang, Guizhou, China.
FAU - Feng, Cheng
AU  - Feng C
AD  - Clinical Medical College, Guizhou Medical University, Guiyang, Guizhou, China.
FAU - Wang, Jishi
AU  - Wang J
AD  - Department of Hematology, Affiliated Hospital of Guizhou Medical University, 
      Guizhou Province Institute of Hematology, Guizhou Province Laboratory of 
      Hematopoietic Stem Cell Transplantation Centre, Guiyang, Guizhou, China.
AD  - National Clinical Research Center for Hematologic Diseases, The First Affiliated 
      Hospital of Soochow University, Soochow, Jiangsu, China.
LA  - eng
PT  - Journal Article
DEP - 20240228
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10933109
OTO - NOTNLM
OT  - acute myeloid leukemia
OT  - drug resistance
OT  - hypoxia-related genes
OT  - immune microenvironment
OT  - risk prognostic model
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/03/14 06:47
MHDA- 2024/03/14 06:48
PMCR- 2024/02/28
CRDT- 2024/03/14 04:18
PHST- 2023/11/16 00:00 [received]
PHST- 2024/02/12 00:00 [accepted]
PHST- 2024/03/14 06:48 [medline]
PHST- 2024/03/14 06:47 [pubmed]
PHST- 2024/03/14 04:18 [entrez]
PHST- 2024/02/28 00:00 [pmc-release]
AID - 1339465 [pii]
AID - 10.3389/fphar.2024.1339465 [doi]
PST - epublish
SO  - Front Pharmacol. 2024 Feb 28;15:1339465. doi: 10.3389/fphar.2024.1339465. 
      eCollection 2024.