title: Upregulated expression of microRNA-214 is linked to tumor progression and adverse prognosis in pediatric osteosarcoma.
abstract: BACKGROUND
  MicroRNA-214 (miR-214) expression has been demonstrated to be dysregulated in human malignancies and to play various roles in tumor progression. While previous study of miRNA expression profiling found that it was one of the most upregulated miRNAs in osteosarcoma signature, the potential role of miR-214 in osteosarcomas has been unclear. Therefore, the aim of this study was to investigate association of miR-214 expression with clinicopathologic features and prognosis in pediatric patients with osteosarcoma.
  
  
  METHODS
  Quantitative real-time reverse transcriptase-polymerase chain reaction analysis was performed to detect expression levels of miR-214 in cancerous and noncancerous bone tissues from 92 children treated for primary osteosarcomas. Then, the clinical significance of miR-214 dysregulation in pediatric osteosarcomas was also determined.
  
  
  RESULTS
  Compared with noncancerous bone tissues, the expression levels of miR-214 were significantly upregulated in osteosarcoma tissues (P < 0.001). High miR-214 expression occurred more frequently in osteosarcoma tissues with large tumor size (P = 0.01), positive metastasis (P = 0.001) and poor response to pre-operative chemotherapy (P = 0.006). Moreover, high miR-214 expression was significantly associated with both shorter overall (P < 0.001) and progression-free survival (PFS; P = 0.001). Multivariate analysis by the Cox proportional hazard model further confirmed that high miR-214 expression was an independent prognostic factor of unfavorable survival in pediatric osteosarcoma (for overall survival: P = 0.008; for PFS: P = 0.01).
  
  
  CONCLUSIONS
  Our data offer evidence that upregulated expression of miR-214 may be linked to tumor progression and adverse prognosis in pediatric osteosarcoma. Further investigation in prospective studies would appear warranted.
authors.affiliation: Pediatric Orthopedic Department, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Haikang
authors.initials: H
authors.lastname: Cai
authors.forename: Lijun
authors.initials: L
authors.lastname: Lin
authors.forename: Mingjie
authors.initials: M
authors.lastname: Tang
authors.forename: Haiqing
authors.initials: H
authors.lastname: Cai
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012516:Osteosarcoma / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: clinicopathologic features; microRNA-214; overall survival; pediatric osteosarcoma; progression-free survival