Medical Oncology

, 30:499 | Cite as

Prognostic evaluation of microRNA-210 expression in pediatric osteosarcoma

  • Haiqing Cai
  • Lijun Lin
  • Haikang Cai
  • Mingjie Tang
  • Zhigang WangEmail author
Original Paper


MicroRNA-210 (miR-210) plays important roles in the regulation of cell growth, angiogenesis, and apoptosis in different cancer type. Previous study of miRNA expression profiling found that miR-210 was significantly elevated in osteosarcoma samples. However, its roles in this disease have not been fully elucidated. Thus, the aim of this study was to investigate the association of miR-210 expression with clinicopathologic features and prognosis in patients with osteosarcomas. Quantitative real-time reverse transcriptase-polymerase chain reaction analysis was performed to detect the expression level of miR-210 in cancerous and noncancerous bone tissues from 92 children treated for primary osteosarcomas. MiR-210 expression was significantly increased in osteosarcoma tissues compared with that in corresponding noncancerous bone tissues (P < 0.001). In addition, miR-210 upregulation more frequently occurred in osteosarcoma tissues with large tumor size (P = 0.02), poor response to preoperative chemotherapy (P = 0.008), and positive metastasis (P = 0.01). Moreover, miR-210 upregulation was associated with significantly decreased overall survival (P = 0.007) and progression-free survival (P = 0.01). In the Cox proportional hazard model, it was confirmed that its expression in the biopsy samples was an independent prognostic factor of unfavorable survival in osteosarcoma (for overall survival: P = 0.01; for progression-free survival: P = 0.02). These findings suggested that miR-210 upregulation showed a strong correlation with tumor aggressive progression of pediatric osteosarcoma and could help prognostic screening of patients with this malignancy.


Pediatric osteosarcoma miR-210 Prognosis Overall survival Progression-free survival 


Conflict of interest



  1. 1.
    Broadhead ML, Clark JC, Myers DE, Dass CR, Choong PF. The molecular pathogenesis of osteosarcoma: a review. Sarcoma. 2011;2011:959248.PubMedCrossRefGoogle Scholar
  2. 2.
    Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009;152:3–13.PubMedCrossRefGoogle Scholar
  3. 3.
    PosthumaDeBoer J, Witlox MA, Kaspers GJ, van Royen BJ. Molecular alterations as target for therapy in metastatic osteosarcoma: a review of literature. Clin Exp Metastasis. 2011;28:493–503.PubMedCrossRefGoogle Scholar
  4. 4.
    Geller DS, Gorlick R. Osteosarcoma: a review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol. 2010;8:705–18.PubMedGoogle Scholar
  5. 5.
    Osman A. MicroRNAs in health and disease–basic science and clinical applications. Clin Lab. 2012;58:393–402.PubMedGoogle Scholar
  6. 6.
    Kong YW, Ferland-McCollough D, Jackson TJ, Bushell M. microRNAs in cancer management. Lancet Oncol. 2012;13:e249–58.PubMedCrossRefGoogle Scholar
  7. 7.
    Subramanian S, Kartha RV. MicroRNA-mediated gene regulations in human sarcomas. Cell Mol Life Sci. 2012;69:3571–85.PubMedCrossRefGoogle Scholar
  8. 8.
    Lulla RR, Costa FF, Bischof JM, Chou PM. de F Bonaldo M, Vanin EF, Soares MB. Identification of Differentially Expressed MicroRNAs in Osteosarcoma. Sarcoma. 2011;2011:732690.PubMedCrossRefGoogle Scholar
  9. 9.
    Fasanaro P, Greco S, Lorenzi M, Pescatori M, Brioschi M, Kulshreshtha R, Banfi C, Stubbs A, Calin GA, Ivan M, Capogrossi MC, Martelli F. An integrated approach for experimental target identification of hypoxia-induced miR-210. J Biol Chem. 2009;284:35134–43.PubMedCrossRefGoogle Scholar
  10. 10.
    Mizuno Y, Tokuzawa Y, Ninomiya Y, Yagi K, Yatsuka-Kanesaki Y, Suda T, Fukuda T, Katagiri T, Kondoh Y, Amemiya T, Tashiro H, Okazaki Y. miR-210 promotes osteoblastic differentiation through inhibition of AcvR1b. FEBS Lett. 2009;583:2263–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Huvos AG. Osteosarcoma in adolescents and young adults: new developments and controversies. Commentary on pathology. Cancer Treat Res. 1993;62:375–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Miller K, Wang M, Gralow J, Dickler M, Cobleigh M, Perez EA, Shenkier T, Cella D, Davidson NE. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med. 2007;357:2666–76.PubMedCrossRefGoogle Scholar
  13. 13.
    Chi JT, Wang Z, Nuyten DS, et al. Gene expression programs in response to hypoxia: cell type specificity and prognostic significance in human cancers. PLoS Med. 2006;3:e47.PubMedCrossRefGoogle Scholar
  14. 14.
    Hong L, Han Y, Zhang H, Zhao Q, Qiao Y. miR-210: a therapeutic target in cancer. Expert Opin Ther Targets. 2013;17:21–8.PubMedCrossRefGoogle Scholar
  15. 15.
    He J, Wu J, Xu N, Xie W, Li M, Li J, Jiang Y, Yang BB, Zhang Y. MiR-210 disturbs mitotic progression through regulating a group of mitosis-related genes. Nucleic Acids Res. 2012 In press.Google Scholar
  16. 16.
    Merlo A, de Quiros SB, Secades P, Zambrano I, Balbín M, Astudillo A, Scola B, Arístegui M, Suarez C, Chiara MD. Identification of a Signaling Axis HIF-1α/MicroRNA-210/ISCU independent of SDH mutation that defines a subgroup of head and neck paragangliomas. J Clin Endocrinol Metab. 2012;97:E2194–200.PubMedCrossRefGoogle Scholar
  17. 17.
    Papaconstantinou IG, Manta A, Gazouli M, Lyberopoulou A, Lykoudis PM, Polymeneas G, Voros D. Expression of MicroRNAs in patients with pancreatic cancer and its prognostic significance. Pancreas. 2012 In press.Google Scholar
  18. 18.
    Hong L, Yang J, Han Y, Lu Q, Cao J, Syed L. High expression of miR-210 predicts poor survival in patients with breast cancer: a meta-analysis. Gene. 2012;507:135–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Võsa U, Vooder T, Kolde R, Vilo J, Metspalu A, Annilo T. Meta-analysis of microrna expression in lung cancer. Int J Cancer. 2012 In press.Google Scholar
  20. 20.
    Wotschofsky Z, Busch J, Jung M, Kempkensteffen C, Weikert S, Schaser KD, Melcher I, Kilic E, Miller K, Kristiansen G, Erbersdobler A, Jung K. Diagnostic and prognostic potential of differentially expressed miRNAs between metastatic and non-metastatic renal cell carcinoma at the time of nephrectomy. Clin Chim Acta. 2012 In press.Google Scholar
  21. 21.
    Wang J, Chen J, Chang P, LeBlanc A, Li D, Abbruzzesse JL, Frazier ML, Killary AM, Sen S. MicroRNAs in plasma of pancreatic ductal adenocarcinoma patients as novel blood-based biomarkers of disease. Cancer Prev Res. 2009;2:807–13.CrossRefGoogle Scholar
  22. 22.
    Rothé F, Ignatiadis M, Chaboteaux C, Haibe-Kains B, Kheddoumi N, Majjaj S, Badran B, Fayyad-Kazan H, Desmedt C, Harris AL, Piccart M, Sotiriou C. Global microRNA expression profiling identifies MiR-210 associated with tumor proliferation, invasion and poor clinical outcome in breast cancer. PLoS ONE. 2011;6:e20980.PubMedCrossRefGoogle Scholar
  23. 23.
    Greither T, Würl P, Grochola L, Bond G, Bache M, Kappler M, Lautenschläger C, Holzhausen HJ, Wach S, Eckert AW, Taubert H. Expression of microRNA 210 associates with poor survival and age of tumor onset of soft-tissue sarcoma patients. Int J Cancer. 2012;130:1230–5.PubMedCrossRefGoogle Scholar
  24. 24.
    Gee HE, Camps C, Buffa FM, Patiar S, Winter SC, Betts G, Homer J, Corbridge R, Cox G, West CM, Ragoussis J, Harris AL. hsa-mir-210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer. Cancer. 2010;116:2148–58.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Haiqing Cai
    • 1
  • Lijun Lin
    • 2
  • Haikang Cai
    • 3
  • Mingjie Tang
    • 4
  • Zhigang Wang
    • 1
    Email author
  1. 1.Pediatric Orthopedic DepartmentShanghai Children’s Medical Center Affiliated to Shanghai Jiaotong University School of MedicineShanghaiChina
  2. 2.Orthopedics DepartmentZhujiang Hospital, The Southern Medical UniversityGuangzhouChina
  3. 3.Orthopaedics DepartmentXuhui central hospitalShanghaiChina
  4. 4.Orthopaedics Department, Shanghai Sixth People’s Hospital, Shanghai Institute for Microsurgery of ExtremitiesShanghai Jiaotong UniversityShanghaiChina

Personalised recommendations