Pediatric Orthopedic Department, Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.
Pediatr Blood Cancer. 2014 Feb;61(2):206-10. doi: 10.1002/pbc.24763. Epub 2013 Sep 9.
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.
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.
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).
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.
MicroRNA-214（miR-214）的表达失调已在人类恶性肿瘤中得到证实，并在肿瘤进展中发挥各种作用。虽然之前的 miRNA 表达谱研究发现它是骨肉瘤特征中上调最明显的 miRNA 之一，但 miR-214 在骨肉瘤中的潜在作用尚不清楚。因此，本研究旨在探讨 miR-214 表达与儿童骨肉瘤患者临床病理特征和预后的关系。
对 92 名接受原发性骨肉瘤治疗的儿童的癌性和非癌性骨组织进行定量实时逆转录聚合酶链反应分析，以检测 miR-214 的表达水平。然后，还确定了 miR-214 失调在儿科骨肉瘤中的临床意义。
与非癌性骨组织相比，骨肉瘤组织中 miR-214 的表达水平显著上调（P<0.001）。miR-214 高表达在肿瘤体积较大（P=0.01）、转移阳性（P=0.001）和术前化疗反应不良的骨肉瘤组织中更为常见（P=0.006）。此外，miR-214 高表达与总生存期（P<0.001）和无进展生存期（PFS；P=0.001）均显著相关。Cox 比例风险模型的多变量分析进一步证实，miR-214 高表达是儿童骨肉瘤不良生存的独立预后因素（总生存期：P=0.008；PFS：P=0.01）。
我们的数据提供了证据，表明 miR-214 的表达上调可能与儿童骨肉瘤的肿瘤进展和不良预后有关。在未来的前瞻性研究中进一步研究似乎是必要的。
