DOI: 10.1101/19007740Oct 3, 2019Paper

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

MedRxiv : the Preprint Server for Health Sciences
C. E. LietzDimitrios Spentzos


Background: There is a lack of well validated biomarkers in osteosarcoma, a rare, recalcitrant disease with variable outcome and poorly understood biologic behavior, for which treatment standards have stalled for decades. The only standard prognostic factor in osteosarcoma remains the amount of pathologic necrosis following pre-operative chemotherapy, which does not adequately capture the biologic complexity of the tumor and has not resulted in optimized patient therapeutic stratification. New, robust biomarkers are needed to understand prognosis and better reflect the underlying biologic and molecular complexity of this disease. Methods: We performed microRNA sequencing in 74 frozen osteosarcoma biopsy samples, the largest single center translationally analyzed cohort to date, and separately analyzed a multi-omic dataset from a large (n = 95) NCI supported national cooperative group cohort. Molecular patterns were tested for association with outcome and used to identify novel therapeutics for further study by integrative pharmacogenomic analysis. Results: MicroRNA profiles were found predict Recurrence Free Survival (5-microRNA profile, Median RFS 59 vs 202 months, log rank p=0.06, HR 1.87, 95% CI 0.96-3.66). The profiles were...Continue Reading

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