Extracellular RNA in a single droplet of human serum reflects physiologic and disease states.
age
biomarker
breast cancer
cancer recurrence
extracellular RNA
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
17 09 2019
17 09 2019
Historique:
pubmed:
5
9
2019
medline:
11
4
2020
entrez:
5
9
2019
Statut:
ppublish
Résumé
Extracellular RNAs (exRNAs) are present in human serum. It remains unclear to what extent these circulating exRNAs may reflect human physiologic and disease states. Here, we developed SILVER-seq (Small Input Liquid Volume Extracellular RNA Sequencing) to efficiently sequence both integral and fragmented exRNAs from a small droplet (5 μL to 7 μL) of liquid biopsy. We calibrated SILVER-seq in reference to other RNA sequencing methods based on milliliters of input serum and quantified droplet-to-droplet and donor-to-donor variations. We carried out SILVER-seq on more than 150 serum droplets from male and female donors ranging from 18 y to 48 y of age. SILVER-seq detected exRNAs from more than a quarter of the human genes, including small RNAs and fragments of mRNAs and long noncoding RNAs (lncRNAs). The detected exRNAs included those derived from genes with tissue (e.g., brain)-specific expression. The exRNA expression levels separated the male and female samples and were correlated with chronological age. Noncancer and breast cancer donors exhibited pronounced differences, whereas donors with or without cancer recurrence exhibited moderate differences in exRNA expression patterns. Even without using differentially expressed exRNAs as features, nearly all cancer and noncancer samples and a large portion of the recurrence and nonrecurrence samples could be correctly classified by exRNA expression values. These data suggest the potential of using exRNAs in a single droplet of serum for liquid biopsy-based diagnostics.
Identifiants
pubmed: 31481608
pii: 1908252116
doi: 10.1073/pnas.1908252116
pmc: PMC6754586
doi:
Substances chimiques
Biomarkers, Tumor
0
Cell-Free Nucleic Acids
0
MicroRNAs
0
RNA, Messenger
0
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
19200-19208Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL108735
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL106579
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL145170
Pays : United States
Organisme : NICHD NIH HHS
ID : K23 HD058799
Pays : United States
Organisme : NHLBI NIH HHS
ID : R00 HL122368
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Conflict of interest statement: A provisional patent is filed. S.Z. is a cofounder of Genemo, Inc.
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