title: Down-regulation of miR-133a and miR-539 are associated with unfavorable prognosis in patients suffering from osteosarcoma.
abstract: BACKGROUND
  MicroRNAs (miRNAs) play key roles in cancer development and progression. The purpose of the present study was to determine the expression levels of miR-133a and miR-539 in osteosarcoma patients and to further investigate the clinicopathological, and prognostic value of these miRNAs.
  
  
  METHODS
  The expression levels of miR-133a and miR-539 were determined by qRT-PCR. Associations between miRNAs expressions and various clinicopathological characteristics were analyzed. Survival rate was determined with Kaplan-Meier and statistically analyzed with the log-rank method between groups. Survival data were evaluated through multivariate Cox regression analysis.
  
  
  RESULTS
  Our findings revealed that the miR-133a expression was significantly decreased in clinical osteosarcoma tissues compared to adjacent normal bone tissues. The expression level of miR-539 was decreased in clinical osteosarcoma tissues as compared to those adjacent normal tissues. Low expressions of miR-133a and miR-539 were significantly association with advanced TNM stage (P = 0.002; P = 0.001), and metastasis or recurrence (P = 0.001; P = 0.01). Furthermore, Kaplan-Meier survival analysis and log-rank test showed that the low expressions of miR-133a and miR-539 were correlated with the reduced overall survival of osteosarcoma patients. Multivariate Cox proportional hazards model showed that decreased expressions of miR-133a and miR-539 (P = 0.007; P = 0.02), TNM stage (P = 0.001; P = 0.002), and metastasis or recurrence (P = 0.005; P = 0.026) were independent prognostic markers of overall survival of patients.
  
  
  CONCLUSIONS
  These results suggest that decreased miR-133a and miR-539 expressions may participate in the progression of osteosarcoma. Together, these results showed that miR-133a and miR-539 may have their role in both progression and prognosis of osteosarcoma.
authors.affiliation: Department of Orthopedics, Qom University of Medical Sciences, Qom, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Mirghasemi
authors.affiliation: Department of Orthopedics Surgery, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Afshin
authors.initials: A
authors.lastname: Taheriazam
authors.affiliation: Department of Anesthesiology, Birjand University of Medical Sciences, Birjand, Iran.
authors.forename: Seyyed Hasan
authors.initials: SH
authors.lastname: Karbasy
authors.affiliation: Department of Orthopedics, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Torkaman
authors.affiliation: Department of Orthopaedic and Trauma Surgery, Birjand University of Medical Sciences, Birjand, Iran.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Shakeri
authors.affiliation: Department of Molecular Biology, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Emad
authors.initials: E
authors.lastname: Yahaghi
authors.affiliation: Cellular & Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran.
authors.forename: Aram
authors.initials: A
authors.lastname: Mokarizadeh
keywords: Cancer; Marker; MicRNA; Patient; Survival