International Journal of Clinical Oncology

, Volume 24, Issue 8, pp 976–982 | Cite as

A four serum-miRNA panel serves as a potential diagnostic biomarker of osteosarcoma

  • Congwei Huang
  • Qinjue Wang
  • Shengshan Ma
  • Yang Sun
  • Ashley Shane Vadamootoo
  • Chengzhe JinEmail author
Original Article



Osteosarcoma (OS) is the most common malignant bone tumor in young adults and adolescents with approximately 3 million new cases annually. Due to the lack of sensitive and specific diagnostic biomarkers, although OS patients are curable after surgical resection, many patients suffer from metastasis or recurrence. This study aimed to investigate whether circulating microRNAs (miRNAs) could serve as biomarkers for the diagnosis of OS.

Materials and methods

Healthy individuals and OS patients enrolled in this study came from Nanjing First Hospital. First, candidate miRNAs were selected by integrated analysis of two GEO datasets and a publicly available miRNA dataset. The expression of these miRNAs in tissues and serum samples were subsequently examined through qRT-PCR. The diagnostic utility of these differential miRNAs was examined by using receiver operating characteristic (ROC) curve analysis. Finally, the potential signaling pathways associated with candidate miRNAs were searched through online tools.


Four miRNAs (miR-487a, miR-493-5p, miR-501-3p and miR-502-5p) were selected to further investigate their diagnostic potential for OS. We discovered miR-487a, miR-493-5p, miR-501-3p and miR-502-5p were upregulated in OS tissues and serums. Besides, miR-487a, miR-493-5p, miR-501-3p and miR-502-5p in peripheral blood of OS patients were tumor-derived. The area under the ROC curve (AUC) was 0.83 (95% CI 0.71–0.97) for miR-487a, 0.79 (95% CI 0.66–0.93) for miR-493-5p, 0.82 (95% CI 0.68–0.95) for miR-501-3p, 0.83 (95% CI 0.72–0.95) for miR-502-5p, and 0.89 (95% CI 0.78–1.0) for miRNAs combination.


Circulating miR-487a, miR-493-5p, miR-501-3p and miR-502-5p were novel potential diagnostic biomarkers of OS.


miRNAs Osteosarcoma GEO database Biomarker 



Funded by Jiangsu Provincial Special Program of Medical Science (BE2016618) and Postgraduate Research & Practice Innovation Program of Jiangsu Province (JX22013459).

Compliance with ethical standards

Conflict of interest

There was no conflict of interest in this work.

Ethical approval

Written informed consent was obtained from all participants, and this study was approved by the Research and Ethical Committee of Nanjing First Hospital.


  1. 1.
    Ma O, Cai WW, Zender L et al (2009) MMP13, Birc2 (cIAP1), and Birc3 (cIAP2), amplified on chromosome 9, collaborate with p53 deficiency in mouse osteosarcoma progression. Cancer Res 69:2559–2567CrossRefGoogle Scholar
  2. 2.
    Kansara M, Teng MW, Smyth MJ et al (2014) Translational biology of osteosarcoma. Nat Rev Cancer 14:722–735CrossRefGoogle Scholar
  3. 3.
    Yang J, Zhang W (2013) New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol 25:398–406CrossRefGoogle Scholar
  4. 4.
    Bielack SS, Kempf-Bielack B, Delling G et al (2002) Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 20:776–790CrossRefGoogle Scholar
  5. 5.
    Gianferante DM, Mirabello L, Savage SA (2017) Germline and somatic genetics of osteosarcoma - connecting aetiology, biology and therapy. Nat Rev Endocrinol 13:480–491CrossRefGoogle Scholar
  6. 6.
    Fabian MR, Sonenberg N, Filipowicz W (2010) Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79:351–379CrossRefGoogle Scholar
  7. 7.
    Mitchell PS, Parkin RK, Kroh EM et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA 105:10513–10518CrossRefGoogle Scholar
  8. 8.
    Bekris LM, Leverenz JB (2015) The biomarker and therapeutic potential of miRNA in Alzheimer's disease. Neurodegener Dis Manag 5:61–74CrossRefGoogle Scholar
  9. 9.
    Li SP, Su HX, Zhao D et al (2016) Plasma miRNA-506 as a Prognostic Biomarker for Esophageal Squamous Cell Carcinoma. Med Sci Monit 22:2195–2201CrossRefGoogle Scholar
  10. 10.
    Tanase C, Albulescu R, Codrici E et al (2015) Circulating biomarker panels for targeted therapy in brain tumors. Future Oncol 11:511–524CrossRefGoogle Scholar
  11. 11.
    Guo L, Luo C, Fan J et al (2015) Serum miRNA profiling identifies miR-150/30a as potential biomarker for workers with damaged nerve fibers from carbon disulfide. Ind Health 53:38–47CrossRefGoogle Scholar
  12. 12.
    Lian F, Cui Y, Zhou C et al (2015) Identification of a plasma four-microRNA panel as potential noninvasive biomarker for osteosarcoma. PLoS ONE 10:e0121499CrossRefGoogle Scholar
  13. 13.
    Nonaka R, Nishimura J, Kagawa Y et al (2014) Circulating miR-199a-3p as a novel serum biomarker for colorectal cancer. Oncol Rep 32:2354–2358CrossRefGoogle Scholar
  14. 14.
    Maciejak A, Kostarska-Srokosz E, Gierlak W et al (2018) Circulating miR-30a-5p as a prognostic biomarker of left ventricular dysfunction after acute myocardial infarction. Sci Rep 8:9883CrossRefGoogle Scholar
  15. 15.
    Yao ZS, Li C, Liang D et al (2018) Diagnostic and prognostic implications of serum miR-101 in osteosarcoma. Cancer Biomark 22:127–133CrossRefGoogle Scholar
  16. 16.
    Kelly AD, Haibe-Kains B, Janeway KA et al (2013) MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32. Genome Med 5:2CrossRefGoogle Scholar
  17. 17.
    Sun L, Chen Y, Su Q et al (2016) Increased plasma miRNA-30a as a biomarker for non-small cell lung cancer. Med Sci Monit 22:647–655CrossRefGoogle Scholar
  18. 18.
    Zhu T, Gao W, Chen X et al (2017) A pilot study of circulating MicroRNA-125b as a diagnostic and prognostic biomarker for epithelial ovarian cancer. Int J Gynecol Cancer 27:3–10CrossRefGoogle Scholar
  19. 19.
    Li C, Li JF, Cai Q et al (2013) MiRNA-199a-3p: A potential circulating diagnostic biomarker for early gastric cancer. J Surg Oncol 108:89–92CrossRefGoogle Scholar
  20. 20.
    Zhou G, Lu M, Chen J et al (2015) Identification of miR-199a-5p in serum as noninvasive biomarkers for detecting and monitoring osteosarcoma. Tumour Biol 36:8845–8852CrossRefGoogle Scholar
  21. 21.
    Xu J, Pan X, Hu Z (2018) MiR-502 mediates esophageal cancer cell TE1 proliferation by promoting AKT phosphorylation. Biochem Biophys Res Commun 501:119–123CrossRefGoogle Scholar
  22. 22.
    Sanches JGP, Xu Y, Yabasin IB et al (2018) miR-501 is upregulated in cervical cancer and promotes cell proliferation, migration and invasion by targeting CYLD. Chem Biol Interact 285:85–95CrossRefGoogle Scholar
  23. 23.
    Zhao J, Xu T, Wang F et al (2017) miR-493-5p suppresses hepatocellular carcinoma cell proliferation through targeting GP73. Biomed Pharmacother 90:744–751CrossRefGoogle Scholar
  24. 24.
    Chang RM, Xiao S, Lei X et al (2017) miRNA-487a promotes proliferation and metastasis in hepatocellular carcinoma. Clin Cancer Res 23:2593–2604CrossRefGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  1. 1.Department of OrthopedicNanjing First Hospital, Nanjing Medical UniversityNanjingChina
  2. 2.Department of OrthopedicLianyungang Hospital Affiliated to Xuzhou Medical UniversityXuzhouChina

Personalised recommendations