title: Cross-species identification of a plasma microRNA signature for detection, therapeutic monitoring, and prognosis in osteosarcoma.
abstract: Osteosarcoma (OS) is the primary bone tumor in children and young adults. Currently, there are no reliable, noninvasive biologic markers to detect the presence or progression of disease, assess therapy response, or provide upfront prognostic insights. MicroRNAs (miRNAs) are evolutionarily conserved, stable, small noncoding RNA molecules that are key posttranscriptional regulators and are ideal candidates for circulating biomarker development due to their stability in plasma, ease of isolation, and the unique expressions associated with specific disease states. Using a qPCR-based platform that analyzes more than 750 miRNAs, we analyzed control and diseased-associated plasma from a genetically engineered mouse model of OS to identify a profile of four plasma miRNAs. Subsequent analysis of 40 human patient samples corroborated these results. We also identified disease-specific endogenous reference plasma miRNAs for mouse and human studies. Specifically, we observed plasma miR-205-5p was decreased 2.68-fold in mice with OS compared to control mice, whereas, miR-214, and miR-335-5p were increased 2.37- and 2.69-fold, respectively. In human samples, the same profile was seen with miR-205-5p decreased 1.75-fold in patients with OS, whereas miR-574-3p, miR-214, and miR-335-5p were increased 3.16-, 8.31- and 2.52-fold, respectively, compared to healthy controls. Furthermore, low plasma levels of miR-214 in metastatic patients at time of diagnosis conveyed a significantly better overall survival. This is the first study to identify plasma miRNAs that could be used to prospectively identify disease, potentially monitor therapeutic efficacy and have prognostic implications for OS patients.
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Wendy
authors.initials: W
authors.lastname: Allen-Rhoades
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Lyazat
authors.initials: L
authors.lastname: Kurenbekova
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Laura
authors.initials: L
authors.lastname: Satterfield
authors.affiliation: Department of Virology and Microbiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Neha
authors.initials: N
authors.lastname: Parikh
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fuja
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Shuck
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Nino
authors.initials: N
authors.lastname: Rainusso
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Matteo
authors.initials: M
authors.lastname: Trucco
authors.affiliation: Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California.
authors.forename: Donald A
authors.initials: DA
authors.lastname: Barkauskas
authors.affiliation: Biostatistics and Informatics Shared Resource, The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Eunji
authors.initials: E
authors.lastname: Jo
authors.affiliation: Biostatistics and Informatics Shared Resource, The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ahern
authors.affiliation: Biostatistics and Informatics Shared Resource, The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
authors.forename: Susan
authors.initials: S
authors.lastname: Hilsenbeck
authors.affiliation: Department of Virology and Microbiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Donehower
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Yustein
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D000818:Animals; D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D002648:Child; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D012372:ROC Curve; D015203:Reproducibility of Results; D059467:Transcriptome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D004317:Doxorubicin
keywords: Biomarker; microRNA; mouse model; osteosarcoma; plasma