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.
Highlights
Osteosarcoma is the most common primary malignant bone tumor predominantly seen in children and adolescents [1]
The expression levels of miR-340 and ROCK1 mRNA in osteosarcoma and corresponding noncancerous bone biopsy samples were detected by quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR), and respectively normalized to RNU6B
Compared with noncancerous bone tissues, miR-340 expression was significantly decreased in osteosarcoma tissues, while ROCK1 expression was significantly increased in osteosarcoma tissues
Summary
Osteosarcoma is the most common primary malignant bone tumor predominantly seen in children and adolescents [1]. While the five-year overall survival rate of patients with osteosarcoma has dramatically improved, to approximately 60%–70% [3], there are a large number of patients who respond poorly to chemotherapy and have a high risk of local relapse or distant metastasis, even after curative resection of the primary tumor and intensive chemotherapy [4]. To address this problem, much work has been performed in an attempt to screen markers with therapeutic implications. It is imperative to identify tumor-derived factors that are associated with the early diagnosis and the prognosis may be helpful to detect chemotherapy-resistant tumors and to generate a modified treatment regimen for this deadly disease
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