A comprehensive characterization of the cell-free transcriptome reveals tissue- and subtype-specific biomarkers for cancer detection.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
21 04 2021
Historique:
received: 03 08 2020
accepted: 10 03 2021
entrez: 22 4 2021
pubmed: 23 4 2021
medline: 4 5 2021
Statut: epublish

Résumé

Cell-free RNA (cfRNA) is a promising analyte for cancer detection. However, a comprehensive assessment of cfRNA in individuals with and without cancer has not been conducted. We perform the first transcriptome-wide characterization of cfRNA in cancer (stage III breast [n = 46], lung [n = 30]) and non-cancer (n = 89) participants from the Circulating Cell-free Genome Atlas (NCT02889978). Of 57,820 annotated genes, 39,564 (68%) are not detected in cfRNA from non-cancer individuals. Within these low-noise regions, we identify tissue- and cancer-specific genes, defined as "dark channel biomarker" (DCB) genes, that are recurrently detected in individuals with cancer. DCB levels in plasma correlate with tumor shedding rate and RNA expression in matched tissue, suggesting that DCBs with high expression in tumor tissue could enhance cancer detection in patients with low levels of circulating tumor DNA. Overall, cfRNA provides a unique opportunity to detect cancer, predict the tumor tissue of origin, and determine the cancer subtype.

Identifiants

pubmed: 33883548
doi: 10.1038/s41467-021-22444-1
pii: 10.1038/s41467-021-22444-1
pmc: PMC8060291
doi:

Substances chimiques

Biomarkers, Tumor 0
Cell-Free Nucleic Acids 0
RNA, Messenger 0

Banques de données

ClinicalTrials.gov
['NCT02889978']

Types de publication

Journal Article Research Support, Non-U.S. Gov't Validation Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

2357

Commentaires et corrections

Type : ErratumIn

Références

Science. 2015 Jan 23;347(6220):1260419
pubmed: 25613900
Oncotarget. 2017 May 3;8(42):71759-71771
pubmed: 29069744
PLoS One. 2015 Aug 28;10(8):e0136133
pubmed: 26317354
Respir Med. 2005 Sep;99(9):1164-74
pubmed: 16085219
Clin Chem. 2002 Oct;48(10):1647-53
pubmed: 12324479
Nat Commun. 2021 Apr 21;12(1):2357
pubmed: 33883548
Cancer Biomark. 2011-2012;10(2):101-7
pubmed: 22430137
Am J Clin Pathol. 2011 Apr;135(4):587-91
pubmed: 21411781
Tumour Biol. 2017 Jul;39(7):1010428317713392
pubmed: 28671019
Nat Cell Biol. 2008 Dec;10(12):1470-6
pubmed: 19011622
Oncotarget. 2019 Apr 23;10(30):2911-2920
pubmed: 31080561
J Biomed Inform. 2019;100S:100001
pubmed: 34384574
Am J Hum Genet. 1999 Jan;64(1):218-24
pubmed: 9915961
Ann Oncol. 2018 Mar 1;29(3):700-706
pubmed: 29216356
Neoplasma. 2008;55(6):549-54
pubmed: 18999886
Tumour Biol. 2017 Jul;39(7):1010428317720212
pubmed: 28720066
Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):5003-8
pubmed: 21383194
Genome Biol. 2014;15(12):550
pubmed: 25516281
Clin Chem. 2013 Jan;59(1):211-24
pubmed: 23065472
Clin Biochem. 1972 Dec;5(4):198-200
pubmed: 4674387
RNA. 2018 Jul;24(7):908-914
pubmed: 29686135
Cell Rep. 2018 Oct 30;25(5):1346-1358
pubmed: 30380423
Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):E5503-12
pubmed: 26392541
Cancer Res. 1996 Feb 15;56(4):860-5
pubmed: 8631025
Expert Rev Mol Diagn. 2019 Jul;19(7):579-590
pubmed: 31215265
Ann Oncol. 2020 Jun;31(6):745-759
pubmed: 33506766
Nat Med. 2014 May;20(5):548-54
pubmed: 24705333
Sci Rep. 2017 Jul 7;7(1):4846
pubmed: 28687783
Clin Chem. 1999 Aug;45(8 Pt 1):1292-4
pubmed: 10430801
Sci Transl Med. 2014 Feb 19;6(224):224ra24
pubmed: 24553385
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Clin Cancer Res. 2018 Jun 15;24(12):2944-2950
pubmed: 29535126
Mol Diagn Ther. 2017 Jun;21(3):259-268
pubmed: 28039578
Exp Lung Res. 2015 Mar;41(2):93-102
pubmed: 25514367
Ann N Y Acad Sci. 2001 Sep;945:172-8
pubmed: 11708475
Ann Oncol. 2020 Mar;31(3):395-403
pubmed: 32067681
Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18761-8
pubmed: 24191000
Ann N Y Acad Sci. 2001 Sep;945:192-4
pubmed: 11708478
Nature. 2018 Nov;563(7732):579-583
pubmed: 30429608
Clin Cancer Res. 1999 Aug;5(8):1961-5
pubmed: 10473072
J Natl Cancer Inst Monogr. 2014 Nov;2014(49):187-97
pubmed: 25417232
Brief Bioinform. 2015 Mar;16(2):205-15
pubmed: 24817567

Auteurs

Matthew H Larson (MH)

GRAIL, Inc., Menlo Park, CA, USA. mlarson@grailbio.com.

Wenying Pan (W)

GRAIL, Inc., Menlo Park, CA, USA.

Hyunsung John Kim (HJ)

GRAIL, Inc., Menlo Park, CA, USA.

Ruth E Mauntz (RE)

GRAIL, Inc., Menlo Park, CA, USA.

Sarah M Stuart (SM)

GRAIL, Inc., Menlo Park, CA, USA.

Monica Pimentel (M)

GRAIL, Inc., Menlo Park, CA, USA.

Yiqi Zhou (Y)

GRAIL, Inc., Menlo Park, CA, USA.

Per Knudsgaard (P)

GRAIL, Inc., Menlo Park, CA, USA.

Vasiliki Demas (V)

GRAIL, Inc., Menlo Park, CA, USA.

Alexander M Aravanis (AM)

GRAIL, Inc., Menlo Park, CA, USA.

Arash Jamshidi (A)

GRAIL, Inc., Menlo Park, CA, USA.

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Classifications MeSH