Open Access Research

MicroRNAs at the human 14q32 locus have prognostic significance in osteosarcoma

Aaron L Sarver1, Venugopal Thayanithy2, Milcah C Scott3, Anne-Marie Cleton-Jansen4, Pancras CW Hogendoorn4, Jaime F Modiano13 and Subbaya Subramanian12*

  • * Corresponding author: Subbaya Subramanian subree@umn.edu

  • † Equal contributors

Author Affiliations

1 Masonic Cancer Center, University of Minnesota, 11-212 Moos Tower , 515 Delaware Street S.E, Minneapolis, MN 55455, USA

2 Department of Surgery, Division of Basic and Translational Research, School of Medicine, University of Minnesota, Minneapolis, MN 55455, USA

3 Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN, 55108, USA

4 Department of Pathology, Leiden University Medical Center, Leiden, 2333ZA, The Netherlands

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Orphanet Journal of Rare Diseases 2013, 8:7  doi:10.1186/1750-1172-8-7

Published: 11 January 2013

Abstract

Background

Deregulation of microRNA (miRNA) transcript levels has been observed in many types of tumors including osteosarcoma. Molecular pathways regulated by differentially expressed miRNAs may contribute to the heterogeneous tumor behaviors observed in naturally occurring cancers. Thus, tumor-associated miRNA expression may provide informative biomarkers for disease outcome and metastatic potential in osteosarcoma patients. We showed previously that clusters of miRNAs at the 14q32 locus are downregulated in human osteosarcoma.

Methods

Human and canine osteosarcoma patient’s samples with clinical follow-up data were used in this study. We used bioinformatics and comparative genomics approaches to identify miRNA based prognostic biomarkers in osteosarcoma. Kaplan-Meier survival curves and Whitney Mann U tests were conducted for validating the statistical significance.

Results

Here we show that an inverse correlation exists between aggressive tumor behavior (increased metastatic potential and accelerated time to death) and the residual expression of 14q32 miRNAs (using miR-382 as a representative of 14q32 miRNAs) in a series of clinically annotated samples from human osteosarcoma patients. We also show a comparable decrease in expression of orthologous 14q32 miRNAs in canine osteosarcoma samples, with conservation of the inverse correlation between aggressive behavior and expression of orthologous miRNA miR-134 and miR-544.

Conclusions

We conclude that downregulation of 14q32 miRNA expression is an evolutionarily conserved mechanism that contributes to the biological behavior of osteosarcoma, and that quantification of representative transcripts from this family, such as miR-382, miR-134, and miR-544, provide prognostic and predictive markers that can assist in the management of patients with this disease.

Keywords:
Bone neoplasm; Prognosis; Integrative analysis; Osteosarcoma; 14q32 miRNAs