TY - JOUR
T1 - Biomarker significance of plasma and tumor miR-21, miR-221, and miR-106a in osteosarcoma
AU - The TARGET osteosarcoma consortium
AU - Nakka, Manjula
AU - Allen-Rhoades, Wendy
AU - Li, Yiting
AU - Kelly, Aaron J.
AU - Shen, Jianhe
AU - Taylor, Aaron M.
AU - Barkauskas, Donald A.
AU - Yustein, Jason T.
AU - Andrulis, Irene L.
AU - Wunder, Jay S.
AU - Gorlick, Richard
AU - Meltzer, Paul S.
AU - Lau, Ching C.
AU - Man, Tsz Kwong
AU - David, Sean
AU - Waterfall, Josh
AU - Bilke, Sven
AU - Smith, Malcolm
AU - Gerhard, Daniela
AU - Auvil, Jaime Guidary
AU - Davidsen, Tanja
AU - Hermida, Leandro
AU - Gesuwan, Patee
AU - Barkauskas, Don
AU - Krailo, Mark
AU - Khanna, Chand
AU - Marina, Neyssa
AU - Teot, Lisa
AU - Gastier-Foster, Julie
AU - Ross, Nicole
AU - Moyer, Yvonne
AU - Monovich, Laura
AU - McNulty, Mary
AU - Andrulis, Irene
AU - Gokgoz, Nalan
AU - Iwata, Shintaro
AU - Ohira, Miki
AU - De Toledo, Silvia Caminada
AU - Petrilli, Sergio
AU - Sun, Jiayi
AU - Taylor, Aaron
N1 - Publisher Copyright:
© Nakka et al.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Biomarker
KW - Osteosarcoma
KW - Plasma
KW - Prognosis
KW - miRNA
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UR - http://www.scopus.com/inward/citedby.url?scp=85030170172&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.18236
DO - 10.18632/oncotarget.18236
M3 - Article
C2 - 29228567
AN - SCOPUS:85030170172
SN - 1949-2553
VL - 8
SP - 96738
EP - 96752
JO - Oncotarget
JF - Oncotarget
IS - 57
ER -