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Int. J. Mol. Sci. 2014, 15(1), 560-573; doi:10.3390/ijms15010560

Combined MicroRNA-340 and ROCK1 mRNA Profiling Predicts Tumor Progression and Prognosis in Pediatric Osteosarcoma

1
Pediatric Orthopedic Department, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai 200031, China
2
Orthopedics Department, Zhujiang Hospital, the Southern Medical University, Guangzhou 510282, China
3
Orthopaedics Department, Xuhui Central Hospital, Shanghai 200233, China
4
Orthopaedics Department, Shanghai Sixth People's Hospital, Shanghai Jiaotong University, Shanghai Institute for Microsurgery of Extremities, Shanghai 200233, China
*
Author to whom correspondence should be addressed.
Received: 29 October 2013 / Revised: 12 December 2013 / Accepted: 23 December 2013 / Published: 6 January 2014
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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.
Keywords: pediatric osteosarcoma; microRNA-340; ROCK1; clinicopathologic features; overall survival; progression-free survival pediatric osteosarcoma; microRNA-340; ROCK1; clinicopathologic features; overall survival; progression-free survival
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Cai, H.; Lin, L.; Cai, H.; Tang, M.; Wang, Z. Combined MicroRNA-340 and ROCK1 mRNA Profiling Predicts Tumor Progression and Prognosis in Pediatric Osteosarcoma. Int. J. Mol. Sci. 2014, 15, 560-573.

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