Genomic and transcriptomic determinants of response to neoadjuvant therapy in rectal cancer.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
received:
24
09
2021
accepted:
29
06
2022
pubmed:
16
8
2022
medline:
23
8
2022
entrez:
15
8
2022
Statut:
ppublish
Résumé
The incidence of rectal cancer is increasing in patients younger than 50 years. Locally advanced rectal cancer is still treated with neoadjuvant radiation, chemotherapy and surgery, but recent evidence suggests that patients with a complete response can avoid surgery permanently. To define correlates of response to neoadjuvant therapy, we analyzed genomic and transcriptomic profiles of 738 untreated rectal cancers. APC mutations were less frequent in the lower than in the middle and upper rectum, which could explain the more aggressive behavior of distal tumors. No somatic alterations had significant associations with response to neoadjuvant therapy in a treatment-agnostic manner, but KRAS mutations were associated with faster relapse in patients treated with neoadjuvant chemoradiation followed by consolidative chemotherapy. Overexpression of IGF2 and L1CAM was associated with decreased response to neoadjuvant therapy. RNA-sequencing estimates of immune infiltration identified a subset of microsatellite-stable immune hot tumors with increased response and prolonged disease-free survival.
Identifiants
pubmed: 35970919
doi: 10.1038/s41591-022-01930-z
pii: 10.1038/s41591-022-01930-z
pmc: PMC9801308
mid: NIHMS1848700
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1646-1655Subventions
Organisme : NCI NIH HHS
ID : T32 CA009501
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA090559
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM132083
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA255574
Pays : United States
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.
Références
Lancet Oncol. 2015 Nov;16(15):1537-1546
pubmed: 26474521
Nat Med. 2015 Nov;21(11):1350-6
pubmed: 26457759
Lancet. 2018 May 26;391(10135):2128-2139
pubmed: 29754777
Mol Oncol. 2021 Oct;15(10):2766-2781
pubmed: 33817986
Sci Transl Med. 2015 Jan 28;7(272):272ra12
pubmed: 25632036
Nat Genet. 2013 Oct;45(10):1127-33
pubmed: 24071851
Ann Oncol. 2015 Feb;26(2):259-71
pubmed: 25214542
BMC Cancer. 2020 Aug 14;20(1):761
pubmed: 32795280
Nature. 2013 Jul 11;499(7457):214-218
pubmed: 23770567
Nucleic Acids Res. 2016 Sep 19;44(16):e131
pubmed: 27270079
Cancer Cell. 2018 Nov 12;34(5):852-862.e4
pubmed: 30393068
Nat Protoc. 2009;4(8):1184-91
pubmed: 19617889
Cancer Cell. 2018 Apr 9;33(4):676-689.e3
pubmed: 29622463
Nat Genet. 2018 Aug;50(8):1189-1195
pubmed: 30013179
Sci Rep. 2017 Nov 30;7(1):16618
pubmed: 29192179
JCO Precis Oncol. 2017 Jul;2017:
pubmed: 28890946
Lancet Oncol. 2012 Aug;13(8):773-81
pubmed: 22805291
Genome Biol. 2014;15(12):550
pubmed: 25516281
Oncotarget. 2022 Jan 05;13:18-31
pubmed: 35018217
Ann Surg. 2005 Jul;242(1):74-82
pubmed: 15973104
BMC Cancer. 2015 Oct 23;15:767
pubmed: 26497495
J Am Coll Surg. 2015 Aug;221(2):430-40
pubmed: 26206642
Nat Cancer. 2020 Jan;1(1):28-45
pubmed: 32656539
Nat Med. 2017 Jun;23(6):703-713
pubmed: 28481359
Cancer Cell. 2018 Apr 9;33(4):721-735.e8
pubmed: 29622466
Science. 2017 Jan 20;355(6322):
pubmed: 28104840
Dis Colon Rectum. 2012 Sep;55(9):990-5
pubmed: 22874607
JAMA Oncol. 2021 Aug 01;7(8):1225-1230
pubmed: 34196693
Ann Surg. 2011 Sep;254(3):486-92; discussion 492-3
pubmed: 21865946
J Gastrointest Surg. 2019 Jul;23(7):1474-1484
pubmed: 30617772
Br J Cancer. 2009 Mar 24;100(6):874-80
pubmed: 19240720
CA Cancer J Clin. 2021 Jan;71(1):7-33
pubmed: 33433946
BMC Cancer. 2020 Apr 6;20(1):288
pubmed: 32252672
J Clin Oncol. 2012 Jan 20;30(3):282-90
pubmed: 22162589
J Natl Compr Canc Netw. 2017 Mar;15(3):411-419
pubmed: 28275039
Nature. 2020 Feb;578(7793):94-101
pubmed: 32025018
Cell Syst. 2015 Dec 23;1(6):417-425
pubmed: 26771021
Clin Trials. 2019 Apr;16(2):165-175
pubmed: 30688523
Cancer Discov. 2012 May;2(5):401-4
pubmed: 22588877
J Pathol. 2013 Sep;231(1):63-76
pubmed: 23836465
Gastroenterology. 2020 Nov;159(5):1975-1978.e4
pubmed: 32730818
Cancer Chemother Pharmacol. 2000;46 Suppl:S52-61
pubmed: 10950149
Immunity. 2018 Apr 17;48(4):812-830.e14
pubmed: 29628290
Nat Rev Gastroenterol Hepatol. 2019 Jun;16(6):361-375
pubmed: 30886395
JCO Precis Oncol. 2017;2017:
pubmed: 30211344
Clin Cancer Res. 2019 Sep 15;25(18):5561-5571
pubmed: 31253631
Clin Cancer Res. 2020 Oct 1;26(19):5198-5207
pubmed: 32669377
Immunity. 2013 Oct 17;39(4):782-95
pubmed: 24138885
Clin Cancer Res. 2021 Jun 1;27(11):2996-3004
pubmed: 33637626
BMC Bioinformatics. 2013 Jan 16;14:7
pubmed: 23323831
Lancet Oncol. 2015 Aug;16(8):957-66
pubmed: 26187751
Ann Surg Oncol. 2016 Aug;23(8):2548-55
pubmed: 27020587
Nature. 2012 Jul 18;487(7407):330-7
pubmed: 22810696
Immunity. 2013 Jul 25;39(1):1-10
pubmed: 23890059
J Surg Oncol. 2016 Oct;114(5):637-641
pubmed: 27641934
Clin Cancer Res. 2020 Jul 1;26(13):3271-3279
pubmed: 32144135
Sci Signal. 2013 Apr 02;6(269):pl1
pubmed: 23550210
Colorectal Dis. 2019 Oct;21(10):1140-1150
pubmed: 31108012
Ann Gastroenterol. 2019 Sep-Oct;32(5):431-440
pubmed: 31474788
J Clin Oncol. 2005 Dec 20;23(36):9257-64
pubmed: 16361623
Cancer Cell. 2018 Jan 8;33(1):125-136.e3
pubmed: 29316426
J Clin Oncol. 1999 Aug;17(8):2396
pubmed: 10561302
Cell. 2018 Apr 5;173(2):321-337.e10
pubmed: 29625050
Bioinformatics. 2014 Apr 1;30(7):1015-6
pubmed: 24371154
JAMA Oncol. 2019 Apr 01;5(4):e185896
pubmed: 30629084
Science. 2017 Jul 28;357(6349):409-413
pubmed: 28596308
Dis Colon Rectum. 2004 Mar;47(3):279-86
pubmed: 14991488
J Mol Diagn. 2015 May;17(3):251-64
pubmed: 25801821
Cancer Discov. 2017 Jun;7(6):610-619
pubmed: 28363909