Based on disulfidptosis-related glycolytic genes to construct a signature for predicting prognosis and immune infiltration analysis of hepatocellular carcinoma.
SLCO1B1
disulfidptosis
glycolysis
hepatocellular carcinoma (HCC)
prognostic signature
subtype
tumor microenvironment
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
12
04
2023
accepted:
04
08
2023
medline:
11
9
2023
pubmed:
8
9
2023
entrez:
8
9
2023
Statut:
epublish
Résumé
Hepatocellular carcinoma (HCC) comprises several distinct molecular subtypes with varying prognostic implications. However, a comprehensive analysis of a prognostic signature for HCC based on molecular subtypes related to disulfidptosis and glycolysis, as well as associated metabolomics and the immune microenvironment, is yet to be fully explored. Based on the differences in the expression of disulfide-related glycolytic genes (DRGGs), patients with HCC were divided into different subtypes by consensus clustering. Establish and verify a risk prognosis signature. Finally, the expression level of the key gene SLCO1B1 in the signature was evaluated using immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) in HCC. The association between this gene and immune cells was explored using multiplex immunofluorescence. The biological functions of the cell counting kit-8, wound healing, and colony formation assays were studied. Different subtypes of patients have specific clinicopathological features, prognosis and immune microenvironment. We identified seven valuable genes and constructed a risk-prognosis signature. Analysis of the risk score revealed that compared to the high-risk group, the low-risk group had a better prognosis, higher immune scores, and more abundant immune-related pathways, consistent with the tumor subtypes. Furthermore, IHC and qRT-PCR analyses showed decreased expression of SLCO1B1 in HCC tissues. Functional experiments revealed that SLCO1B1 overexpression inhibited the proliferation, migration, and invasion of HCC cells. We developed a prognostic signature that can assist clinicians in predicting the overall survival of patients with HCC and provides a reference value for targeted therapy.
Sections du résumé
Background
Hepatocellular carcinoma (HCC) comprises several distinct molecular subtypes with varying prognostic implications. However, a comprehensive analysis of a prognostic signature for HCC based on molecular subtypes related to disulfidptosis and glycolysis, as well as associated metabolomics and the immune microenvironment, is yet to be fully explored.
Methods
Based on the differences in the expression of disulfide-related glycolytic genes (DRGGs), patients with HCC were divided into different subtypes by consensus clustering. Establish and verify a risk prognosis signature. Finally, the expression level of the key gene SLCO1B1 in the signature was evaluated using immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) in HCC. The association between this gene and immune cells was explored using multiplex immunofluorescence. The biological functions of the cell counting kit-8, wound healing, and colony formation assays were studied.
Results
Different subtypes of patients have specific clinicopathological features, prognosis and immune microenvironment. We identified seven valuable genes and constructed a risk-prognosis signature. Analysis of the risk score revealed that compared to the high-risk group, the low-risk group had a better prognosis, higher immune scores, and more abundant immune-related pathways, consistent with the tumor subtypes. Furthermore, IHC and qRT-PCR analyses showed decreased expression of SLCO1B1 in HCC tissues. Functional experiments revealed that SLCO1B1 overexpression inhibited the proliferation, migration, and invasion of HCC cells.
Conclusion
We developed a prognostic signature that can assist clinicians in predicting the overall survival of patients with HCC and provides a reference value for targeted therapy.
Identifiants
pubmed: 37680641
doi: 10.3389/fimmu.2023.1204338
pmc: PMC10482091
doi:
Substances chimiques
SLCO1B1 protein, human
0
Liver-Specific Organic Anion Transporter 1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1204338Informations de copyright
Copyright © 2023 Wang, Chen, Zhang, Chen, Peng and Huang.
Déclaration de conflit d'intérêts
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.
Références
Theranostics. 2021 Jan 1;11(7):3089-3108
pubmed: 33537076
Bioinformatics. 2012 Mar 15;28(6):882-3
pubmed: 22257669
J Immunother Cancer. 2022 May;10(5):
pubmed: 35618286
Genome Res. 2018 Nov;28(11):1747-1756
pubmed: 30341162
Oncol Lett. 2018 May;15(5):6562-6570
pubmed: 29725404
Int J Oncol. 2001 Jun;18(6):1265-9
pubmed: 11351261
Comput Struct Biotechnol J. 2019 May 23;17:661-674
pubmed: 31205619
Nat Rev Gastroenterol Hepatol. 2019 Oct;16(10):589-604
pubmed: 31439937
PLoS One. 2014 Sep 17;9(9):e107468
pubmed: 25229481
Nature. 2019 Aug;572(7769):397-401
pubmed: 31367041
Front Immunol. 2023 Mar 31;14:1171420
pubmed: 37063886
Biol Direct. 2023 Feb 7;18(1):4
pubmed: 36750831
Neoplasma. 2001;48(4):307-12
pubmed: 11712684
Front Immunol. 2021 Nov 04;12:750046
pubmed: 34804034
J Gastrointest Oncol. 2022 Aug;13(4):1959-1966
pubmed: 36092319
Br J Cancer. 2017 Nov 7;117(10):1518-1528
pubmed: 28926527
Cancer Res. 2015 Jun 15;75(12):2510-9
pubmed: 25908587
J Pharmacol Exp Ther. 2019 Mar;368(3):363-381
pubmed: 30578287
Cell Mol Biol Lett. 2022 Dec 6;27(1):106
pubmed: 36474147
Front Immunol. 2023 Feb 23;14:1081572
pubmed: 36911723
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Front Immunol. 2022 Jan 05;12:781087
pubmed: 35069553
J Clin Oncol. 2007 Jun 20;25(18):2586-93
pubmed: 17577038
Biochemistry. 2012 Aug 28;51(34):6804-15
pubmed: 22852582
Nat Rev Gastroenterol Hepatol. 2022 Jan;19(1):26-44
pubmed: 34504325
Cell Biochem Funct. 2012 Apr;30(3):198-204
pubmed: 22095390
Nat Cell Biol. 2023 Mar;25(3):375-376
pubmed: 36918690
Gut. 2022 Mar;71(3):616-626
pubmed: 33563643
Cancer Res. 2018 Dec 1;78(23):6575-6580
pubmed: 30154154
Nucleic Acids Res. 1988 Mar 11;16(5):1681-2
pubmed: 3353218
Biomed Pharmacother. 2023 Aug;164:114902
pubmed: 37209628
Acta Pharm Sin B. 2022 Mar;12(3):1163-1185
pubmed: 35530162
Br J Pharmacol. 2016 Mar;173(6):970-9
pubmed: 26750865
Nat Rev Gastroenterol Hepatol. 2019 Jun;16(6):361-375
pubmed: 30886395
J Clin Pharm Ther. 2022 Dec;47(12):2049-2067
pubmed: 35896189
Exp Hematol Oncol. 2021 May 10;10(1):31
pubmed: 33971970
BMC Cancer. 2022 Feb 5;22(1):142
pubmed: 35123420
Gut. 2019 Nov;68(11):2019-2031
pubmed: 31227589
Hepatol Int. 2023 Aug;17(4):889-903
pubmed: 36930410
Front Pharmacol. 2020 Sep 25;11:571143
pubmed: 33101029
Methods. 2001 Dec;25(4):402-8
pubmed: 11846609
Am J Transl Res. 2020 Aug 15;12(8):4141-4159
pubmed: 32913494
Immunity. 2013 Jul 25;39(1):1-10
pubmed: 23890059
N Engl J Med. 2017 Oct 12;377(15):1409-1412
pubmed: 29020592
Front Immunol. 2023 May 30;14:1198878
pubmed: 37325625
Acta Pharm Sin B. 2022 Feb;12(2):558-580
pubmed: 35256934
Nat Cell Biol. 2023 Mar;25(3):404-414
pubmed: 36747082
Nat Cell Biol. 2020 Apr;22(4):476-486
pubmed: 32231310
Nat Rev Gastroenterol Hepatol. 2022 Apr;19(4):257-273
pubmed: 35022608
Protein Cell. 2021 Aug;12(8):599-620
pubmed: 33000412
J Exp Clin Cancer Res. 2020 Jul 6;39(1):126
pubmed: 32631382
Cell. 2017 Jun 15;169(7):1342-1356.e16
pubmed: 28622514
Antioxid Redox Signal. 2011 Jun 15;14(12):2581-642
pubmed: 21275844
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Science. 2018 Apr 27;360(6387):449-453
pubmed: 29599194
Cell Death Dis. 2020 Oct 23;11(10):902
pubmed: 33097691
Nat Rev Dis Primers. 2016 Apr 14;2:16018
pubmed: 27158749