Characterization of pancreatic cancer with ultra-low tumor mutational burden.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 03 2023
16 03 2023
Historique:
received:
06
01
2023
accepted:
14
03
2023
entrez:
17
3
2023
pubmed:
18
3
2023
medline:
22
3
2023
Statut:
epublish
Résumé
In pancreatic cancer (PC), Tumor mutation burden (TMB) has been reported to be lower than in other cancers, with its clinical significance remaining unclear. We analyzed the dataset of whole-exome sequencing and gene expression profiling of 93 resected PC cases. The median TMB was 0.24. The TMB was classified as High (≥ 5.0), Low (< 5.0, ≥ 1.0), or Ultra-low (< 1.0). Nineteen samples (20%) were classified as TMB-low, and 74 (80%) were classified as TMB-ultra-low; no samples were TMB-high. TMB-ultra-low PC had significantly fewer borderline resectable lesions (P = 0.028) and fewer adenosquamous carcinomas (P = 0.003) than TBM-low PC. Furthermore, the TMB-ultra-low PC showed significantly lower detection rates of driver mutations and copy number variations. Microsatellite instability was not significantly correlated with the TMB status. The TMB-ultra-low PC had a significantly better prognosis than TBM-low PC (P = 0.023). A multivariate analysis identified TMB-ultra-low PC as an independent favorable prognostic factor (hazard ratio, 2.11; P = 0.019). A gene expression analysis showed that TMB-ultra-low PC was associated with reduced TP53 inactivation (P = 0.003) and reduced chromosomal instability (P = 0.001) compared to TBM-low PC. TMB-ultra-low PC had specific gene expression signatures and a better prognosis than TMB-low PC.
Identifiants
pubmed: 36928600
doi: 10.1038/s41598-023-31579-8
pii: 10.1038/s41598-023-31579-8
pmc: PMC10020557
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4359Informations de copyright
© 2023. The Author(s).
Références
N Engl J Med. 2014 Dec 4;371(23):2189-2199
pubmed: 25409260
J Clin Invest. 2017 Aug 1;127(8):2930-2940
pubmed: 28650338
J Med Cases. 2022 May;13(5):240-243
pubmed: 35655630
Ann Transl Med. 2019 Nov;7(22):640
pubmed: 31930041
Cell. 2015 Jan 15;160(1-2):48-61
pubmed: 25594174
Cancer Discov. 2020 Dec;10(12):1808-1825
pubmed: 33139244
Nat Med. 2019 Mar;25(3):517-525
pubmed: 30664780
Cancer Immunol Res. 2016 Nov;4(11):959-967
pubmed: 27671167
Nat Genet. 2020 Mar;52(3):331-341
pubmed: 32025003
J Natl Compr Canc Netw. 2021 Apr 1;19(4):439-457
pubmed: 33845462
Cancer Cell. 2017 Aug 14;32(2):185-203.e13
pubmed: 28810144
Nature. 2013 Aug 22;500(7463):415-21
pubmed: 23945592
Pancreas. 2017 Mar;46(3):335-340
pubmed: 28099251
World J Surg. 2012 Dec;36(12):2888-94
pubmed: 22907393
Cell Rep. 2019 Jul 30;28(5):1370-1384.e5
pubmed: 31365877
Nature. 2013 Jul 11;499(7457):214-218
pubmed: 23770567
Science. 2015 Apr 3;348(6230):124-8
pubmed: 25765070
J Immunother Cancer. 2017 May 16;5:44
pubmed: 28515944
Ann Oncol. 2019 Jul 1;30(7):1096-1103
pubmed: 31038663
Eur J Cancer. 2022 Jul;169:64-73
pubmed: 35512587
J Clin Oncol. 2019 Feb 1;37(4):318-327
pubmed: 30557521
Pancreas. 2019 Oct;48(9):1232-1236
pubmed: 31609933
Nature. 2012 Feb 08;482(7385):400-4
pubmed: 22318521
Lancet Oncol. 2020 Oct;21(10):1353-1365
pubmed: 32919526
Cold Spring Harb Perspect Med. 2016 Aug 01;6(8):
pubmed: 27329033
JAMA Oncol. 2018 Mar 08;4(3):e173420
pubmed: 29098284
Nature. 2017 Nov 23;551(7681):512-516
pubmed: 29132146
Anticancer Res. 2022 Jul;42(7):3537-3549
pubmed: 35790264
Nat Commun. 2015 Apr 09;6:6744
pubmed: 25855536
Am J Pathol. 2002 Jan;160(1):91-9
pubmed: 11786403
Nature. 2020 Jun;582(7810):100-103
pubmed: 32461694
Genome Med. 2017 Apr 19;9(1):34
pubmed: 28420421
Biomed Res. 2014;35(6):407-12
pubmed: 25743347
Gastroenterology. 2019 May;156(7):2056-2072
pubmed: 30660727
Nature. 2020 Jun;582(7810):95-99
pubmed: 32494066
Science. 2018 Oct 12;362(6411):
pubmed: 30309915
Nat Rev Cancer. 2021 Jun;21(6):379-392
pubmed: 33727690
Biomed Res. 2016;37(1):51-62
pubmed: 26912140
N Engl J Med. 2017 Dec 21;377(25):2500-2501
pubmed: 29262275
Ann Oncol. 2019 Jan 1;30(1):44-56
pubmed: 30395155
Cancer Res. 2012 Mar 1;72(5):1081-91
pubmed: 22237626
Lancet. 2016 Jul 16;388(10041):248-57
pubmed: 27265347
Nat Genet. 2006 Sep;38(9):1043-8
pubmed: 16921376
Surg Today. 2019 Oct;49(10):809-819
pubmed: 30980180
Cancer Sci. 2020 Feb;111(2):687-699
pubmed: 31863614
Science. 2017 Jul 28;357(6349):409-413
pubmed: 28596308
Nat Genet. 2019 Feb;51(2):202-206
pubmed: 30643254
Biomed Res. 2018;39(3):159-167
pubmed: 29899191
J Gastrointest Oncol. 2018 Dec;9(6):1014-1026
pubmed: 30603120
Cancer Sci. 2020 Oct;111(10):3893-3901
pubmed: 32662546
Cancer Sci. 2019 Aug;110(8):2620-2628
pubmed: 31152682