MicroRNA-mRNA networks define translatable molecular outcome phenotypes in osteosarcoma.

Autor: Lietz CE; Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Garbutt C; Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.; Illumina, Inc., San Diego, United States., Barry WT; Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, United States., Deshpande V; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Chen YL; Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Lozano-Calderon SA; Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Wang Y; Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, United States.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, United States., Lawney B; Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, United States.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, United States., Ebb D; Pediatric Hematology-Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Cote GM; Department of Hematology/Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Duan Z; Department of Orthopaedic Surgery, UCLA, Los Angeles, CA, United States., Hornicek FJ; Department of Orthopaedic Surgery, UCLA, Los Angeles, CA, United States., Choy E; Department of Hematology/Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Petur Nielsen G; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States., Haibe-Kains B; Department of Medical Biophysics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada., Quackenbush J; Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, United States.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States.; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, United States., Spentzos D; Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States. dspentzos@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Mar 10; Vol. 10 (1), pp. 4409. Date of Electronic Publication: 2020 Mar 10.
DOI: 10.1038/s41598-020-61236-3
Abstrakt: 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.
Databáze: MEDLINE