Copy-Number Alteration Burden Differentially Impacts Immune Profiles and Molecular Features of Hepatocellular Carcinoma.
Aged
Antigen-Presenting Cells
/ immunology
Antigens, Neoplasm
/ immunology
Biomarkers, Tumor
/ genetics
Carcinoma, Hepatocellular
/ genetics
Chromosomal Instability
DNA Copy Number Variations
DNA Methylation
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms
/ genetics
Male
Middle Aged
Mutation
Phenotype
Prognosis
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 12 2020
01 12 2020
Historique:
received:
20
04
2020
revised:
08
07
2020
accepted:
28
08
2020
pubmed:
3
9
2020
medline:
15
12
2021
entrez:
3
9
2020
Statut:
ppublish
Résumé
Chromosomal instability is a hallmark of cancer that results in broad and focal copy-number alterations (CNAs), two events associated with distinct molecular, immunologic, and clinical features. In hepatocellular carcinoma (HCC), the role of CNAs has not been thoroughly assessed. Thus, we dissected the impact of CNA burdens on HCC molecular and immune features. We analyzed SNP array data from 452 paired tumor/adjacent resected HCCs and 25 dysplastic nodules. For each sample, broad and focal CNA burdens were quantified using CNApp, and the resulting broad scores (BS) and focal scores (FS) were correlated with transcriptomic, mutational, and methylation profiles, tumor immune composition, and clinicopathologic data. HCCs with low broad CNA burdens (defined as BS ≤ 4; 17%) presented high inflammation, active infiltrate signaling, high cytolytic activity, and enrichment of the "HCC immune class" and gene signatures related to antigen presentation. Conversely, tumors with chromosomal instability (high broad CNA loads, BS ≥ 11; 40%), displayed immune-excluded traits and were linked to proliferation, HCCs with high chromosomal instability exhibit features of immune exclusion, whereas tumors displaying low burdens of broad CNAs present an immune active profile. These CNA scores can be tested to predict response to immunotherapies.
Identifiants
pubmed: 32873569
pii: 1078-0432.CCR-20-1497
doi: 10.1158/1078-0432.CCR-20-1497
pmc: PMC7710584
mid: NIHMS1626291
doi:
Substances chimiques
Antigens, Neoplasm
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
6350-6361Subventions
Organisme : Cancer Research UK
ID : 26813
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA196521
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK076986
Pays : United States
Organisme : Cancer Research UK
ID : C9380/A26813
Pays : United Kingdom
Informations de copyright
©2020 American Association for Cancer Research.
Références
Cell. 2017 Feb 9;168(4):707-723
pubmed: 28187290
Oncoimmunology. 2018 Oct 19;7(12):e1526613
pubmed: 30524909
Nat Rev Clin Oncol. 2018 Oct;15(10):599-616
pubmed: 30061739
Lancet. 2017 Jun 24;389(10088):2492-2502
pubmed: 28434648
Cancer Res. 2008 Aug 15;68(16):6779-88
pubmed: 18701503
Nat Genet. 2020 Jun;52(6):582-593
pubmed: 32483290
Nat Genet. 2015 May;47(5):505-511
pubmed: 25822088
Nat Med. 2020 Jun;26(6):909-918
pubmed: 32472114
Hepatology. 2008 Jun;47(6):2059-67
pubmed: 18506891
Nat Commun. 2013;4:2612
pubmed: 24113773
Nat Rev Dis Primers. 2016 Apr 14;2:16018
pubmed: 27158749
Science. 2015 Apr 3;348(6230):124-8
pubmed: 25765070
Nat Rev Cancer. 2019 Jun;19(6):307-325
pubmed: 31092904
N Engl J Med. 2017 Jun 1;376(22):2109-2121
pubmed: 28445112
Elife. 2018 Dec 11;7:
pubmed: 30526857
Nat Med. 2006 Apr;12(4):410-6
pubmed: 16532004
Cancer Cell. 2018 Apr 9;33(4):676-689.e3
pubmed: 29622463
Lancet Oncol. 2018 Jul;19(7):940-952
pubmed: 29875066
Elife. 2020 Jan 15;9:
pubmed: 31939734
N Engl J Med. 2015 Nov 12;373(20):1984
pubmed: 26559592
Nat Rev Genet. 2020 Jan;21(1):44-62
pubmed: 31548659
Cell. 2015 Jan 15;160(1-2):48-61
pubmed: 25594174
Nat Genet. 2012 May 06;44(6):694-8
pubmed: 22561517
Hepatology. 2010 Apr;51(4):1401-9
pubmed: 20054870
Cell. 2017 Jun 15;169(7):1327-1341.e23
pubmed: 28622513
Science. 2017 Jan 20;355(6322):
pubmed: 28104840
Gut. 2020 Feb;69(2):355-364
pubmed: 30979717
J Clin Invest. 2006 Jun;116(6):1582-95
pubmed: 16710476
Nature. 2014 Nov 27;515(7528):568-71
pubmed: 25428505
Cancer Res. 2009 Sep 15;69(18):7385-92
pubmed: 19723656
Cancer Invest. 2018;36(6):338-348
pubmed: 30136875
Nat Rev Clin Oncol. 2018 Mar;15(3):139-150
pubmed: 29297505
J Hepatol. 2011 Dec;55(6):1325-31
pubmed: 21703203
J Hepatol. 2017 Dec;67(6):1222-1231
pubmed: 28843658
Cancer Manag Res. 2019 Apr 01;11:2605-2616
pubmed: 31114327
Hepatology. 2015 Jun;61(6):1945-56
pubmed: 25645722
J Hepatol. 2019 Jan;70(1):58-65
pubmed: 30213589
Int J Cancer. 2019 Apr 15;144(8):1941-1953
pubmed: 30350310
Gastroenterology. 2017 Sep;153(3):812-826
pubmed: 28624577
Science. 2016 Mar 25;351(6280):1463-9
pubmed: 26940869
Immunity. 2018 Apr 17;48(4):812-830.e14
pubmed: 29628290
Nat Commun. 2019 Sep 19;10(1):4278
pubmed: 31537801
Lancet Oncol. 2017 Aug;18(8):1009-1021
pubmed: 28694034
Cell Rep. 2017 Jan 3;18(1):248-262
pubmed: 28052254
Clin Cancer Res. 2019 Apr 1;25(7):2021-2023
pubmed: 30617138
Curr Opin Cell Biol. 2020 Apr;63:135-143
pubmed: 32092639
Gastroenterology. 2011 May;140(5):1501-12.e2
pubmed: 21320499
Sci Transl Med. 2017 Mar 1;9(379):
pubmed: 28251903
Clin Cancer Res. 2020 Aug 15;26(16):4381-4389
pubmed: 32269054
Cell. 2018 Apr 5;173(2):291-304.e6
pubmed: 29625048
Cancer Res. 2017 Jul 1;77(13):3540-3550
pubmed: 28487385
Nature. 2019 Mar;567(7749):479-485
pubmed: 30894752