Prognostic value of novel immune-related genomic biomarkers identified in head and neck squamous cell carcinoma.
head and neck neoplasms
immunity
tumor biomarkers
tumor microenvironment
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
07 2020
07 2020
Historique:
accepted:
01
06
2020
entrez:
29
7
2020
pubmed:
29
7
2020
medline:
21
9
2021
Statut:
ppublish
Résumé
The immune response within the tumor microenvironment plays a key role in tumorigenesis and determines the clinical outcomes of head and neck squamous cell carcinoma (HNSCC). However, to date, a paucity of robust, reliable immune-related biomarkers has been identified that are capable of estimating prognosis in HNSCC patients. High-throughput RNA sequencing was performed in tumors and matched adjacent tissues from five HNSCC patients, and the immune signatures expression of 730 immune-related transcripts selected from the nCounter PanCancer Immune Profiling Panel were assessed. Survival analyzes were performed in a training cohort, consisting of 416 HNSCC cases, retrieved from The Cancer Genome Atlas (TCGA) database. A prognostic signature was built, using elastic net-penalized Cox regression and backward, stepwise Cox regression analyzes. The outcomes were validated by an independent cohort of 115 HNSCC patients, using tissue microarrays and immunohistochemistry staining. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was also used to estimate the relative fractions of 22 immune-cell types and their correlations coefficients with prognostic biomarkers. Collectively, 248 immune-related genes were differentially expressed in paired tumors and normal tissues using RNA sequencing. After process screening in the training TCGA cohort, four immune-related genes ( The well-established model encompassing both immune-related biomarkers and clinicopathological factor might serve as a promising tool for the prognostic prediction of HNSCC.
Sections du résumé
BACKGROUND
The immune response within the tumor microenvironment plays a key role in tumorigenesis and determines the clinical outcomes of head and neck squamous cell carcinoma (HNSCC). However, to date, a paucity of robust, reliable immune-related biomarkers has been identified that are capable of estimating prognosis in HNSCC patients.
METHODS
High-throughput RNA sequencing was performed in tumors and matched adjacent tissues from five HNSCC patients, and the immune signatures expression of 730 immune-related transcripts selected from the nCounter PanCancer Immune Profiling Panel were assessed. Survival analyzes were performed in a training cohort, consisting of 416 HNSCC cases, retrieved from The Cancer Genome Atlas (TCGA) database. A prognostic signature was built, using elastic net-penalized Cox regression and backward, stepwise Cox regression analyzes. The outcomes were validated by an independent cohort of 115 HNSCC patients, using tissue microarrays and immunohistochemistry staining. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was also used to estimate the relative fractions of 22 immune-cell types and their correlations coefficients with prognostic biomarkers.
RESULTS
Collectively, 248 immune-related genes were differentially expressed in paired tumors and normal tissues using RNA sequencing. After process screening in the training TCGA cohort, four immune-related genes (
CONCLUSIONS
The well-established model encompassing both immune-related biomarkers and clinicopathological factor might serve as a promising tool for the prognostic prediction of HNSCC.
Identifiants
pubmed: 32719094
pii: jitc-2019-000444
doi: 10.1136/jitc-2019-000444
pmc: PMC7390201
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.
Références
N Engl J Med. 2016 Nov 10;375(19):1856-1867
pubmed: 27718784
J Cell Mol Med. 2017 Sep;21(9):2199-2210
pubmed: 28401653
J Clin Oncol. 2015 Oct 10;33(29):3293-304
pubmed: 26351330
Nat Methods. 2015 May;12(5):453-7
pubmed: 25822800
Front Cell Dev Biol. 2019 Apr 09;7:52
pubmed: 31024913
J Immunother Cancer. 2019 Nov 27;7(1):325
pubmed: 31775882
Lancet Oncol. 2010 Aug;11(8):781-9
pubmed: 20451455
Nat Commun. 2019 Sep 27;10(1):4404
pubmed: 31562303
J Immunother Cancer. 2015 Dec 15;3:42
pubmed: 26674611
CA Cancer J Clin. 2017 Jan;67(1):51-64
pubmed: 28076666
JAMA Oncol. 2016 Nov 1;2(11):1490-1495
pubmed: 27491050
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Nat Commun. 2013;4:2612
pubmed: 24113773
Cancer Res. 2013 Mar 15;73(6):1733-41
pubmed: 23288508
Nat Rev Clin Oncol. 2015 Jan;12(1):11-26
pubmed: 25403939
Cell Physiol Biochem. 2018;50(4):1429-1440
pubmed: 30355951
Oncoimmunology. 2015 Aug 12;5(2):e1071007
pubmed: 27057436
Nat Rev Genet. 2018 Feb;19(2):93-109
pubmed: 29279605
Semin Cancer Biol. 2018 Oct;52(Pt 2):228-240
pubmed: 29355614
Nature. 2015 Jan 29;517(7536):576-82
pubmed: 25631445
J Clin Invest. 2017 Aug 1;127(8):2930-2940
pubmed: 28650338
Blood. 2015 Sep 24;126(13):1555-64
pubmed: 26194763
J Immunother Cancer. 2017 May 16;5:44
pubmed: 28515944
Mol Cancer. 2017 Mar 29;16(1):70
pubmed: 28356111
Cell Mol Immunol. 2019 Jan;16(1):40-52
pubmed: 30275538
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
Cell. 2018 Nov 1;175(4):984-997.e24
pubmed: 30388455
Blood. 2018 May 31;131(22):2454-2465
pubmed: 29650799
Nat Rev Immunol. 2015 Nov;15(11):669-82
pubmed: 26471778
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Nat Rev Cancer. 2018 May;18(5):269-282
pubmed: 29497144
CA Cancer J Clin. 2019 Jan;69(1):7-34
pubmed: 30620402
Cell. 2015 Sep 10;162(6):1365-78
pubmed: 26359988
Immunity. 2018 Apr 17;48(4):812-830.e14
pubmed: 29628290
Science. 2009 May 15;324(5929):938-41
pubmed: 19443782
Head Neck Oncol. 2013 Feb 27;5(3):24
pubmed: 24723971
Cell Physiol Biochem. 2017;44(2):804-816
pubmed: 29176322
JCI Insight. 2016 Oct 20;1(17):e89829
pubmed: 27777979
Cancer Res. 2013 Jan 1;73(1):128-38
pubmed: 23135914
Clin Cancer Res. 2018 Jan 1;24(1):6-13
pubmed: 28751445