MicroRNA-mRNA networks define translatable molecular outcome phenotypes in osteosarcoma

Scientific Reports
Christopher E LietzDimitrios Spentzos

Abstract

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.

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Citations

May 25, 2021·Frontiers in Molecular Biosciences·Sandra BrasilVanessa Dos Reis Ferreira

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Methods Mentioned

BETA
surgical resection
biopsy
biopsies
RNAseq
RNA seq
Assay
Chip

Clinical Trials Mentioned

NCT02124772
NCT03458728

Software Mentioned

PharmacoDB Batch Query
DAVID
ArrayTools
Ensembl
Therapeutically Applicable Research to Generate Effective Trea...
methylumi R
PharmacoDB
PharmacoGx
R
BioCarta

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