MicroRNA-mRNA networks define translatable molecular outcome phenotypes in osteosarcoma.
Adolescent
Adult
Aged
Biomarkers, Tumor
/ genetics
Biopsy
Bone Neoplasms
/ genetics
Child
Child, Preschool
Cohort Studies
Female
Gene Regulatory Networks
Humans
Machine Learning
Male
MicroRNAs
/ genetics
Middle Aged
Osteosarcoma
/ genetics
Phenotype
Prognosis
RNA, Messenger
/ genetics
Sequence Analysis, RNA
/ methods
Survival Analysis
Young Adult
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
10 03 2020
10 03 2020
Historique:
received:
17
11
2019
accepted:
03
02
2020
entrez:
12
3
2020
pubmed:
12
3
2020
medline:
15
12
2020
Statut:
epublish
Résumé
There is a lack of well validated prognostic biomarkers in osteosarcoma, a rare, recalcitrant disease for which treatment standards have not changed in over 20 years. We performed microRNA sequencing in 74 frozen osteosarcoma biopsy samples, constituting the largest single center translationally analyzed osteosarcoma cohort to date, and we separately analyzed a multi-omic dataset from a large NCI supported national cooperative group cohort. We validated the prognostic value of candidate microRNA signatures and contextualized them in relevant transcriptomic and epigenomic networks. Our results reveal the existence of molecularly defined phenotypes associated with outcome independent of clinicopathologic features. Through machine learning based integrative pharmacogenomic analysis, the microRNA biomarkers identify novel therapeutics for stratified application in osteosarcoma. The previously unrecognized osteosarcoma subtypes with distinct clinical courses and response to therapy could be translatable for discerning patients appropriate for more intensified, less intensified, or alternate therapeutic regimens.
Identifiants
pubmed: 32157112
doi: 10.1038/s41598-020-61236-3
pii: 10.1038/s41598-020-61236-3
pmc: PMC7064533
doi:
Substances chimiques
Biomarkers, Tumor
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
4409Subventions
Organisme : NCI NIH HHS
ID : R01 CA178908
Pays : United States
Organisme : U.S. Department of Health & Human Services | National Institutes of Health (NIH)
ID : R35CA220523
Pays : International
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