title: Combined microRNA-340 and ROCK1 mRNA profiling predicts tumor progression and prognosis in pediatric osteosarcoma.
abstract: To investigate the association of combined microRNA-340 (miR-340) and ROCK1 mRNA profiling with clinicopathologic features and prognosis in pediatric patients with osteosarcoma. Quantitative real-time reverse transcriptase-polymerase chain reaction analysis was performed to detect expression levels of miR-340 and ROCK1 mRNA in cancerous and noncancerous bone tissues from 92 children treated for primary osteosarcomas. Compared with noncancerous bone tissues, the expression levels of miR-340 and ROCK1 mRNA were, respectively, downregulated and upregulated in osteosarcoma tissues (both p < 0.001), which was consistent with the results of in situ hybridization and immunohistochemistry analysis. The downregulation of miR-340 was negatively correlated with the upregulation of ROCK1 mRNA in osteosarcoma tissues (r = -0.78, p = 0.001). In addition, the combined miR-340 downregulation and ROCK1 upregulation (miR-340-low/ROCK1-high) occurred more frequently in osteosarcoma tissues with positive metastasis (p < 0.001) and poor response to pre-operative chemotherapy (p = 0.002). Moreover, miR-340-low/ROCK1-high expression was significantly associated with both shortest overall survival (p < 0.001) and progression-free survival (p < 0.001). Multivariate analysis further confirmed that miR-340-low/ROCK1-high expression was an independent prognostic factor of unfavorable survival in pediatric osteosarcoma (for overall survival: p = 0.006, for progression-free survival: p = 0.008). Our data offer convincing evidence, for the first time, that the combined miR-340 downregulation and ROCK1 upregulation may be linked to tumor progression and adverse prognosis in pediatric osteosarcoma.
authors.affiliation: Pediatric Orthopedic Department, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200031, China. gangqing@vip.sina.com.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Cai
authors.affiliation: Pediatric Orthopedic Department, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200031, China. linlijun1@126.com.
authors.forename: Lijun
authors.initials: L
authors.lastname: Lin
authors.affiliation: Pediatric Orthopedic Department, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200031, China. caihaikang@163.com.
authors.forename: Haikang
authors.initials: H
authors.lastname: Cai
authors.affiliation: Pediatric Orthopedic Department, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200031, China. 13311828153@189.cn.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Tang
authors.affiliation: Pediatric Orthopedic Department, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200031, China. wzgchq@163.com.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D012516:Osteosarcoma / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult; D054460:rho-Associated Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C570046:MIRN340 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases