Biomarker significance of plasma and tumor miR-21, miR-221, and miR-106a in osteosarcoma
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Manjula Nakka1,2, Wendy Allen-Rhoades1,2,4, Yiting Li1,2, Aaron J. Kelly2,3, Jianhe Shen1,2, Aaron M. Taylor2,3, Donald A. Barkauskas5,6, Jason T. Yustein1,2,4, Irene L. Andrulis7,8, Jay S. Wunder9, Richard Gorlick6, Paul S. Meltzer10, Ching C. Lau1,2,3,4 and Tsz-Kwong Man1,2,3,4, the TARGET osteosarcoma consortium*
1Texas Children’s Cancer and Hematology Centers, Texas Children’s Hospital, Houston, TX, USA
2Department of Pediatrics, and Baylor College of Medicine, Houston, TX, USA
3Program of Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX, USA
4Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA
5Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
6Children’s Oncology Group, Monrovia, CA, USA
7Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada
8Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
9Department of Surgery, University of Toronto, Toronto, ON, Canada
10Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
*Ching Lau, Paul Meltzer, Sean David, Josh Waterfall, Sven Bilke, Malcolm Smith, Daniela Gerhard, Jaime Guidary Auvil, Tanja Davidsen, Leandro Hermida, Patee Gesuwan, Richard Gorlick, Don Barkauskas, Mark Krailo, Chand Khanna, Neyssa Marina, Lisa Teot, Julie Gastier-Foster, Nicole Ross, Yvonne Moyer, Laura Monovich, Mary McNulty, Irene Andrulis, Nalan Gokgoz, Shintaro Iwata, Miki Ohira, Silvia Caminada De Toledo, Sergio Petrilli, Jiayi Sun, Aaron Taylor, Jianhe Shen and Tsz-Kwong Man
Tsz-Kwong Man, email: [email protected]
Keywords: miRNA, osteosarcoma, biomarker, plasma, prognosis
Received: December 09, 2016 Accepted: May 15, 2017 Published: May 27, 2017
Osteosarcoma is the most common malignant bone tumor in children and young adults. Despite the use of surgery and multi-agent chemotherapy, osteosarcoma patients who have a poor response to chemotherapy or develop relapses have a dismal outcome. Identification of biomarkers for active disease may help to monitor tumor burden, detect early relapses, and predict prognosis in these patients. In this study, we examined whether circulating miRNAs can be used as biomarkers in osteosarcoma patients. We performed genome-wide miRNA profiling on a discovery cohort of osteosarcoma and control plasma samples. A total of 56 miRNAs were upregulated and 164 miRNAs were downregulated in osteosarcoma samples when compared to control plasma samples. miR-21, miR-221 and miR-106a were selected for further validation based on their known biological importance. We showed that all three circulating miRNAs were expressed significantly higher in osteosarcoma samples than normal samples in an independent cohort obtained from the Children’s Oncology Group. Furthermore, we demonstrated that miR-21 was expressed significantly higher in osteosarcoma tumors compared with normal bone controls. More importantly, lower expressions of miR-21 and miR-221, but not miR-106a, significantly correlated with a poor outcome. In conclusion, our results indicate that miR-21, miR-221 and miR-106a were elevated in the circulation of osteosarcoma patients, whereas tumor expressions of miR-21 and miR-221 are prognostically significant. Further investigation of these miRNAs may lead to a better prognostic method and potential miRNA therapeutics for osteosarcoma.
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