Comprehensive exploration of the involvement of cuproptosis in tumorigenesis and progression of neuroblastoma.
Cell cycle
Cuproptosis
Neuroblastoma (NB)
PDHA1
Tumor immune microenvironment (TIME)
Journal
BMC genomics
ISSN: 1471-2164
Titre abrégé: BMC Genomics
Pays: England
ID NLM: 100965258
Informations de publication
Date de publication:
27 Nov 2023
27 Nov 2023
Historique:
received:
16
04
2023
accepted:
26
09
2023
medline:
29
11
2023
pubmed:
28
11
2023
entrez:
27
11
2023
Statut:
epublish
Résumé
Copper-induced cell death, or "cuproptosis," as an apoptotic process, has recently received much attention in human diseases. Recent studies on cuproptosis have provided novel insights into the pathogenesis of various diseases, especially cancers. However, the association between neuroblastoma (NB) and cuproptosis in terms of their clinical outcomes, tumorigenesis, and treatment response remains unclear. To determine the role of cuproptosis in NB tumorigenesis and progression, this study employed a systematic technique to explore the characteristic patterns of 10 key cuproptosis-related genes (CUGs) in NB. Consensus clustering analysis of the TARGET and GEO databases divided the NB patients into two subgroups that showed different clinicopathological attributes, molecular patterns, survival outcomes, disease-associated pathways, tumor immune microenvironment (TIME) features, and treatment responses. Moreover, a cuproptosis scoring scheme was established, which divided the patients with NB into two groups with high scores and low scores as per the median score. Furthermore, this research developed a nomogram and risk signature on the basis of this cuproptosis score to better elucidate its function in predicting NB prognosis. In vitro experiments were carried out using Transwell Assay, HLECs tube formation assay, Colony formation assay, Western Blotting Assay, Immunohistochemical (IHC) Staining, Immunofluorescence (IF) Staining and Flow Cytometry Analysis. The results demonstrated that the established cuproptosis score and prediction model could effectively distinguish between the individuals in low and high-risk groups and had a high predictive value. Lastly, bioinformatics analysis and in vitro experiments enabled the identification of PDHA1, a key CUG, which was involved in both DNA replication-related pathways and the cell cycle. It was also associated with tumorigenesis and progression of NB. Cuproptosis, especially PDHA1, play a crucial role in the TIME characteristics, tumor progression, and long-term prognosis of NB. The patterns of cuproptosis assessed in this research may improve the understanding of the overall concept of NB tumorigenesis, thus facilitating the development of more effective therapeutic interventions.
Sections du résumé
BACKGROUND
BACKGROUND
Copper-induced cell death, or "cuproptosis," as an apoptotic process, has recently received much attention in human diseases. Recent studies on cuproptosis have provided novel insights into the pathogenesis of various diseases, especially cancers. However, the association between neuroblastoma (NB) and cuproptosis in terms of their clinical outcomes, tumorigenesis, and treatment response remains unclear.
METHODS
METHODS
To determine the role of cuproptosis in NB tumorigenesis and progression, this study employed a systematic technique to explore the characteristic patterns of 10 key cuproptosis-related genes (CUGs) in NB. Consensus clustering analysis of the TARGET and GEO databases divided the NB patients into two subgroups that showed different clinicopathological attributes, molecular patterns, survival outcomes, disease-associated pathways, tumor immune microenvironment (TIME) features, and treatment responses. Moreover, a cuproptosis scoring scheme was established, which divided the patients with NB into two groups with high scores and low scores as per the median score. Furthermore, this research developed a nomogram and risk signature on the basis of this cuproptosis score to better elucidate its function in predicting NB prognosis. In vitro experiments were carried out using Transwell Assay, HLECs tube formation assay, Colony formation assay, Western Blotting Assay, Immunohistochemical (IHC) Staining, Immunofluorescence (IF) Staining and Flow Cytometry Analysis.
RESULTS
RESULTS
The results demonstrated that the established cuproptosis score and prediction model could effectively distinguish between the individuals in low and high-risk groups and had a high predictive value. Lastly, bioinformatics analysis and in vitro experiments enabled the identification of PDHA1, a key CUG, which was involved in both DNA replication-related pathways and the cell cycle. It was also associated with tumorigenesis and progression of NB.
CONCLUSION
CONCLUSIONS
Cuproptosis, especially PDHA1, play a crucial role in the TIME characteristics, tumor progression, and long-term prognosis of NB. The patterns of cuproptosis assessed in this research may improve the understanding of the overall concept of NB tumorigenesis, thus facilitating the development of more effective therapeutic interventions.
Identifiants
pubmed: 38012558
doi: 10.1186/s12864-023-09699-2
pii: 10.1186/s12864-023-09699-2
pmc: PMC10680286
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
715Subventions
Organisme : Guangzhou Municipal Science and Technology Project
ID : 202102010236
Organisme : Guangzhou Municipal Science and Technology Project
ID : 202102010170
Organisme : Guangzhou Municipal Science and Technology Project
ID : 202201011843
Organisme : Research foundation of Guangzhou Women and Children's Medical Center for Clinical Doctor
ID : GWCMC2020LH-4-004
Organisme : Basic and Applied Basic Research Foundation of Guangdong Province
ID : 2021A1515010860
Organisme : National Natural Science Foundation of China
ID : 82103544
Informations de copyright
© 2023. The Author(s).
Références
Nature. 2008 Oct 16;455(7215):930-5
pubmed: 18724359
Front Immunol. 2022 Aug 04;13:958368
pubmed: 35990642
Cancer Biomark. 2017 Dec 6;20(4):589-596
pubmed: 28800318
Nature. 2008 Oct 16;455(7215):975-8
pubmed: 18923525
J Clin Oncol. 2015 Sep 20;33(27):3008-17
pubmed: 26304901
Eur J Immunol. 2022 Sep;52(9):1441-1451
pubmed: 35775327
Nat Rev Dis Primers. 2016 Nov 10;2:16078
pubmed: 27830764
Front Immunol. 2022 Jul 29;13:919231
pubmed: 35967366
Oncogene. 1998 Dec 17;17(24):3137-43
pubmed: 9872329
Cancer Res. 2019 Sep 15;79(18):4557-4566
pubmed: 31350295
Front Mol Biosci. 2022 Mar 04;9:841814
pubmed: 35309510
Nat Genet. 2013 Mar;45(3):279-84
pubmed: 23334666
Front Cell Dev Biol. 2021 Aug 17;9:668947
pubmed: 34485273
Cancer Lett. 1996 Jul 12;104(2):183-92
pubmed: 8665486
Pediatr Blood Cancer. 2021 May;68 Suppl 2:e28473
pubmed: 33818884
Nat Rev Clin Oncol. 2012 May 15;9(7):391-9
pubmed: 22585002
Front Immunol. 2022 Jul 11;13:925618
pubmed: 35898502
Nature. 2008 Oct 16;455(7215):967-70
pubmed: 18923523
J Cell Physiol. 2021 Jan;236(1):294-308
pubmed: 32510620
Cell Res. 2022 May;32(5):417-418
pubmed: 35354936
Lancet. 2007 Jun 23;369(9579):2106-20
pubmed: 17586306
Front Pharmacol. 2022 Aug 08;13:947372
pubmed: 36003495
Clin Cancer Res. 2021 Jul 1;27(13):3507-3509
pubmed: 33947691
Cancers (Basel). 2021 May 14;13(10):
pubmed: 34069127
Cancer Lett. 2003 Jul 18;197(1-2):125-30
pubmed: 12880971
Science. 2022 Mar 18;375(6586):1254-1261
pubmed: 35298263
Front Immunol. 2022 Nov 28;13:1054305
pubmed: 36518756
Cancers (Basel). 2022 Aug 18;14(16):
pubmed: 36010978
Pathol Res Pract. 2019 Mar;215(3):478-482
pubmed: 30611622
Sci Rep. 2022 Jul 5;12(1):11325
pubmed: 35790864
Clin Cancer Res. 2010 Sep 1;16(17):4353-62
pubmed: 20719933
Front Pharmacol. 2022 Jun 28;13:930041
pubmed: 35837286
J Clin Oncol. 2006 Dec 20;24(36):5725-34
pubmed: 17179106
N Engl J Med. 2010 Jun 10;362(23):2202-11
pubmed: 20558371
Nat Rev Clin Oncol. 2022 Aug;19(8):515-533
pubmed: 35614230
Front Oncol. 2022 Jul 22;12:927706
pubmed: 35936736