Circulating Tumor Cell Transcriptomics as Biopsy Surrogates in Metastatic Breast Cancer.
Journal
Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840
Informations de publication
Date de publication:
May 2022
May 2022
Historique:
received:
03
09
2021
accepted:
11
10
2021
pubmed:
10
1
2022
medline:
12
4
2022
entrez:
9
1
2022
Statut:
ppublish
Résumé
Metastatic breast cancer (MBC) and the circulating tumor cells (CTCs) leading to macrometastases are inherently different than primary breast cancer. We evaluated whether whole transcriptome RNA-Seq of CTCs isolated via an epitope-independent approach may serve as a surrogate for biopsies of macrometastases. We performed RNA-Seq on fresh metastatic tumor biopsies, CTCs, and peripheral blood (PB) from 19 newly diagnosed MBC patients. CTCs were harvested using the ANGLE Parsortix microfluidics system to isolate cells based on size and deformability, independent of a priori knowledge of cell surface marker expression. Gene expression separated CTCs, metastatic biopsies, and PB into distinct groups despite heterogeneity between patients and sample types. CTCs showed higher expression of immune oncology targets compared with corresponding metastases and PB. Predictive biomarker (n = 64) expression was highly concordant for CTCs and metastases. Repeat observation data post-treatment demonstrated changes in the activation of different biological pathways. Somatic single nucleotide variant analysis showed increasing mutational complexity over time. We demonstrate that RNA-Seq of CTCs could serve as a surrogate biomarker for breast cancer macrometastasis and yield clinically relevant insights into disease biology and clinically actionable targets.
Sections du résumé
BACKGROUND
BACKGROUND
Metastatic breast cancer (MBC) and the circulating tumor cells (CTCs) leading to macrometastases are inherently different than primary breast cancer. We evaluated whether whole transcriptome RNA-Seq of CTCs isolated via an epitope-independent approach may serve as a surrogate for biopsies of macrometastases.
METHODS
METHODS
We performed RNA-Seq on fresh metastatic tumor biopsies, CTCs, and peripheral blood (PB) from 19 newly diagnosed MBC patients. CTCs were harvested using the ANGLE Parsortix microfluidics system to isolate cells based on size and deformability, independent of a priori knowledge of cell surface marker expression.
RESULTS
RESULTS
Gene expression separated CTCs, metastatic biopsies, and PB into distinct groups despite heterogeneity between patients and sample types. CTCs showed higher expression of immune oncology targets compared with corresponding metastases and PB. Predictive biomarker (n = 64) expression was highly concordant for CTCs and metastases. Repeat observation data post-treatment demonstrated changes in the activation of different biological pathways. Somatic single nucleotide variant analysis showed increasing mutational complexity over time.
CONCLUSION
CONCLUSIONS
We demonstrate that RNA-Seq of CTCs could serve as a surrogate biomarker for breast cancer macrometastasis and yield clinically relevant insights into disease biology and clinically actionable targets.
Identifiants
pubmed: 35000083
doi: 10.1245/s10434-021-11135-2
pii: 10.1245/s10434-021-11135-2
pmc: PMC8989945
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2882-2894Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR001854
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA014089
Pays : United States
Organisme : NCI NIH HHS
ID : P30CA014089
Pays : United States
Organisme : ANGLE plc.
ID : Personal grant to J.E.L.
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
© 2022. The Author(s).
Références
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
J Clin Oncol. 2013 Nov 1;31(31):3997-4013
pubmed: 24101045
Nat Commun. 2016 Feb 01;7:10346
pubmed: 26831747
Br J Cancer. 2005 Aug 22;93(4):387-91
pubmed: 16106245
Mol Cell Biol. 2011 Jul;31(13):2577-90
pubmed: 21536646
J Hematol Oncol. 2019 May 14;12(1):48
pubmed: 31088479
Cold Spring Harb Symp Quant Biol. 2005;70:149-58
pubmed: 16869748
Cancer Res. 2014 Mar 15;74(6):1694-704
pubmed: 24599131
N Engl J Med. 2020 Feb 13;382(7):597-609
pubmed: 31825569
Int J Cancer. 2016 Jun 15;138(12):2894-904
pubmed: 26789903
Nat Methods. 2013 Nov;10(11):1081-2
pubmed: 24037244
BMC Genomics. 2006 Feb 24;7:35
pubmed: 16504121
Nat Med. 2019 Dec;25(12):1928-1937
pubmed: 31768066
N Engl J Med. 2004 Aug 19;351(8):781-91
pubmed: 15317891
Int J Mol Sci. 2017 Aug 31;18(9):
pubmed: 28858218
Sci Rep. 2019 Feb 6;9(1):1482
pubmed: 30728399
Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Genome Res. 2011 Jul;21(7):1160-7
pubmed: 21543516
Mol Oncol. 2015 Nov;9(9):1773-82
pubmed: 26093818
Oncotarget. 2015 Dec 29;6(42):44623-34
pubmed: 26556851
PeerJ. 2018 Jul 31;6:e5362
pubmed: 30083469
Cancer Res. 2011 Dec 15;71(24):7705-15
pubmed: 22037876
Cancer Res. 2016 Jul 1;76(13):3690-701
pubmed: 27197177
Genome Res. 2018 Nov;28(11):1747-1756
pubmed: 30341162
Crit Rev Oncol Hematol. 2012 Dec;84(3):301-13
pubmed: 22710198
Arch Pathol Lab Med. 2010 Jul;134(7):e48-72
pubmed: 20586616
Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20826-31
pubmed: 18087040
Cell. 2019 Jan 10;176(1-2):98-112.e14
pubmed: 30633912
Cancer Treat Rev. 2018 Feb;63:40-47
pubmed: 29207310
J Intern Med. 2013 Aug;274(2):113-26
pubmed: 23844915
Nature. 2019 Feb;566(7745):553-557
pubmed: 30728496
Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2730-5
pubmed: 21482774
Oncotarget. 2018 Jan 11;9(6):7036-7053
pubmed: 29467948
Cold Spring Harb Perspect Med. 2017 Aug 1;7(8):
pubmed: 28289245
Cancers (Basel). 2019 Sep 30;11(10):
pubmed: 31575023
Cancer Cell. 2017 Aug 14;32(2):169-184.e7
pubmed: 28810143
Ann Surg Oncol. 2018 Aug;25(8):2261-2270
pubmed: 29868978
N Engl J Med. 2017 Aug 10;377(6):523-533
pubmed: 28578601
Cell Mol Immunol. 2021 Apr;18(4):1074-1076
pubmed: 33462382
J Clin Invest. 2018 Apr 2;128(4):1371-1383
pubmed: 29480819
Genome Med. 2020 Mar 19;12(1):31
pubmed: 32192534
Cytometry A. 2018 Dec;93(12):1234-1239
pubmed: 30107082
J Exp Med. 2020 Aug 3;217(8):
pubmed: 32644115
Cancer Cell. 2016 Apr 11;29(4):452-463
pubmed: 27070700