Combined elevation of microRNA-196a and microRNA-196b in sera predicts unfavorable prognosis in patients with osteosarcomas

Int J Mol Sci. 2014 Apr 17;15(4):6544-55. doi: 10.3390/ijms15046544.

Abstract

Aim: To investigate whether the aberrant expression of microRNA (miR)-196a and miR-196b can be used as potential prognostic markers of human osteosarcoma.

Methods: Quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis was performed to detect the expression levels of miR-196a and miR-196b in osteosarcoma tissues and patients' sera.

Results: Expression levels of miR-196a and miR-196b in osteosarcoma tissues were both significantly higher than those in noncancerous bone tissues (both p<0.001), in line with which, the serum levels of the two miRNAs were also markedly upregulated in patients with osteosarcomas compared with healthy controls (both p<0.001). Then, the elevation of serum miR-196a and miR-196b levels both more frequently occurred in osteosarcoma patients with high tumor grade (p=0.008 and 0.01, respectively), positive metastasis (p=0.001 and 0.006, respectively) and recurrence (p=0.001 and 0.006, respectively). Moreover, high serum miR-196a, high serum miR-196b and conjoined expression of miR-196a/miR-196b were all independent prognostic factors for OS (overall survival) and DFS (disease-free survival) of osteosarcoma patients.

Conclusion: Our present data indicate the involvement of miR-196a and miR-196b upregulation in the pathogenesis of osteosarcoma. More importantly, the altered levels of circulating miR-196a and miR-196b might have great potential to serve as novel and non-invasive prognostic factors for this malignancy.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Bone Neoplasms / diagnosis
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / genetics
  • Disease-Free Survival
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / blood*
  • Odds Ratio
  • Osteosarcoma / diagnosis
  • Osteosarcoma / drug therapy
  • Osteosarcoma / genetics
  • Prognosis
  • Recurrence
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • MIRN196 microRNA, human
  • MicroRNAs