Identification of prognostic biomarkers and correlations with immune infiltrates among cGAS-STING in hepatocellular carcinoma.
Antineoplastic Agents
/ pharmacology
Biomarkers, Tumor
/ antagonists & inhibitors
Carcinoma, Hepatocellular
/ drug therapy
Datasets as Topic
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Immunity, Innate
/ drug effects
Kaplan-Meier Estimate
Liver
/ immunology
Liver Neoplasms
/ drug therapy
Lymphocytes, Tumor-Infiltrating
/ immunology
Membrane Proteins
/ metabolism
Nucleotidyltransferases
/ metabolism
Oligonucleotide Array Sequence Analysis
Prognosis
RNA-Seq
Signal Transduction
/ drug effects
cGAS-STING
hepatocellular carcinoma
prognosis
tumor-infiltrating
Journal
Bioscience reports
ISSN: 1573-4935
Titre abrégé: Biosci Rep
Pays: England
ID NLM: 8102797
Informations de publication
Date de publication:
30 10 2020
30 10 2020
Historique:
received:
21
07
2020
revised:
13
09
2020
accepted:
02
10
2020
pubmed:
3
10
2020
medline:
15
4
2021
entrez:
2
10
2020
Statut:
ppublish
Résumé
The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway induces innate immunity by activating the production of inflammatory cytokines and type I interferons. Recently, studies revealed that self-DNA from by-products of chromosome instability and tumors could activate the cGAS-STING pathway, and subsequently promote or inhibit tumor development. However, the prognostic value and correlations with immune infiltrates of the cGAS-STING pathway in hepatocellular carcinoma (HCC) have not been clarified. In the present study, we used the Molecular Signatures Database, Oncomine, UALCAN, Human Protein Atlas, Kaplan-Meier plotter, LinkedOmics, and Tumor Immune Estimation Resource databases. Overexpression of XRCC5, IRF3, TRIM21, STAT6, DDX41, TBK1, XRCC6, TREX1, PRKDC, and TMEM173 was markedly correlated with clinical stages and pathological grades in HCC. Moreover, higher mRNA expression of XRCC5, XRCC6, and PRKDC was significantly related with shorter overall survival. However, higher mRNA expression of IFI16, STAT6, NLRC3, and TMEM173 was associated with favorable overall survival. Our results suggested that the kinase targets of the cGAS-STING pathway included the SRC family of tyrosine kinases (LCK and LYN), phosphoinositide 3-kinase-related protein kinase (PIKK) family kinases (ATM and ATR), and mitogen-activated protein kinase 1 (MAPK1). Furthermore, we identified significant correlations among the expression of cGAS-STING pathway and infiltration of B cells, CD4+T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in HCC. The expression of the cGAS-STING pathway also exhibited strong relationships with diverse immune marker sets in HCC. These findings suggest that cGAS-STING pathway members may be used as prognostic biomarkers and immunotherapeutic targets HCC patients.
Identifiants
pubmed: 33006365
pii: 226566
doi: 10.1042/BSR20202603
pmc: PMC7569205
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Biomarkers, Tumor
0
Membrane Proteins
0
STING1 protein, human
0
Nucleotidyltransferases
EC 2.7.7.-
cGAS protein, human
EC 2.7.7.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2020 The Author(s).
Références
Nat Cell Biol. 2019 Dec;21(12):1604-1614
pubmed: 31792381
Cell Mol Life Sci. 2008 Oct;65(19):3058-73
pubmed: 18563293
Lancet. 2018 Mar 31;391(10127):1301-1314
pubmed: 29307467
PLoS One. 2014 Aug 01;9(8):e103609
pubmed: 25084355
Science. 2015 Mar 13;347(6227):aaa2630
pubmed: 25636800
Nat Commun. 2014 Oct 10;5:5166
pubmed: 25300616
Immunity. 2014 Mar 20;40(3):329-41
pubmed: 24560620
J Cell Biochem. 2010 May;110(1):210-8
pubmed: 20213763
Nature. 2019 May;569(7758):718-722
pubmed: 31118511
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Neoplasia. 2004 Jan-Feb;6(1):1-6
pubmed: 15068665
Nature. 2016 Aug 18;536(7616):359
pubmed: 26982724
Carcinogenesis. 2011 Apr;32(4):530-6
pubmed: 21304054
Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12498-503
pubmed: 9770514
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Nat Med. 2018 Aug;24(8):1143-1150
pubmed: 30038220
Nat Immunol. 2010 Nov;11(11):997-1004
pubmed: 20890285
Proc Natl Acad Sci U S A. 2017 Jun 6;114(23):E4612-E4620
pubmed: 28533362
Cancer Res. 2017 Nov 1;77(21):e108-e110
pubmed: 29092952
Mol Ther. 2008 Nov;16(11):1789-97
pubmed: 18781139
Hepatology. 2007 Apr;45(4):938-47
pubmed: 17393520
Oncotarget. 2016 Aug 2;7(31):49322-49333
pubmed: 27384994
Br J Cancer. 2019 Apr;120(9):896-902
pubmed: 30944458
Gastroenterology. 2018 Dec;155(6):1971-1984.e4
pubmed: 30213555
Sci Rep. 2018 Jun 15;8(1):9227
pubmed: 29907753
J Biol Chem. 2014 May 2;289(18):12313-29
pubmed: 24634213
Mol Med. 2009 Mar-Apr;15(3-4):85-94
pubmed: 19098997
J Clin Oncol. 2007 Jul 20;25(21):3069-75
pubmed: 17634485
Biomed Pharmacother. 2017 Aug;92:1-6
pubmed: 28525794
Neoplasia. 2017 Aug;19(8):649-658
pubmed: 28732212
Gut. 2015 May;64(5):842-8
pubmed: 25666193
Cancer Discov. 2020 Jan;10(1):26-39
pubmed: 31852718
Nat Immunol. 2011 Sep 04;12(10):959-65
pubmed: 21892174
Mol Biol Cell. 2002 Jun;13(6):1929-39
pubmed: 12058060
Cancer Res. 2010 Dec 15;70(24):10202-12
pubmed: 21159642
Biochim Biophys Acta. 2015 Nov;1852(11):2494-503
pubmed: 26303640
Nat Rev Genet. 2019 Nov;20(11):657-674
pubmed: 31358977
Eur Rev Med Pharmacol Sci. 2019 Sep;23(18):7835-7847
pubmed: 31599408
Oncogene. 2020 Feb;39(8):1652-1664
pubmed: 31740782
Immunity. 2014 Nov 20;41(5):830-42
pubmed: 25517615
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Nature. 2009 Nov 5;462(7269):108-12
pubmed: 19847166
J Hematol Oncol. 2018 Sep 14;11(1):115
pubmed: 30217218
J Immunol. 2012 Nov 1;189(9):4258-65
pubmed: 23018462
Lancet. 2017 Jan 7;389(10064):56-66
pubmed: 27932229
Aging (Albany NY). 2019 Jan 20;11(2):480-500
pubmed: 30661062
J Med Genet. 2016 Jan;53(1):24-33
pubmed: 26510428
Cell Death Dis. 2020 May 7;11(5):326
pubmed: 32382015
Nat Immunol. 2016 Sep 20;17(10):1142-9
pubmed: 27648547
Int J Biol Macromol. 2020 Mar 1;146:497-507
pubmed: 31923489
Biomed Pharmacother. 2017 Nov;95:55-61
pubmed: 28826097
Science. 2013 Feb 15;339(6121):826-30
pubmed: 23258412
Immunity. 2013 Oct 17;39(4):782-95
pubmed: 24138885
Onco Targets Ther. 2019 Sep 26;12:7923-7928
pubmed: 31920325
J Exp Med. 2018 Feb 5;215(2):699-718
pubmed: 29339449
Clin Cancer Res. 2011 Sep 1;17(17):5546-52
pubmed: 21670084
Genome Biol. 2016 Aug 22;17(1):174
pubmed: 27549193
J Clin Oncol. 2012 Jul 20;30(21):2678-83
pubmed: 22711850
DNA Repair (Amst). 2004 Aug-Sep;3(8-9):1197-205
pubmed: 15279808
Autophagy. 2013 Jun 1;9(6):925-7
pubmed: 23518600
Cell Prolif. 2017 Dec;50(6):
pubmed: 28990231
Nucleic Acids Res. 2018 Jan 4;46(D1):D956-D963
pubmed: 29136207