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微小 RNA-183/Ezrin 轴在判断骨肉瘤患者预后中的临床意义。

Clinical significance of microRNA-183/Ezrin axis in judging the prognosis of patients with osteosarcoma.

机构信息

Department of Orthopedics Spine Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, 830000, Xinjiang, China.

出版信息

Med Oncol. 2014 Feb;31(2):821. doi: 10.1007/s12032-013-0821-3. Epub 2013 Dec 19.

Abstract

MicroRNA-183 (miR-183) has been demonstrated to be a tumor suppressor miRNA in inhibition of migration and invasion of osteosarcoma by targeting an oncogene Ezrin. The aim of the present study was to determine the correlation of combined miR-183 and Ezrin mRNA expression with clinicopathologic features and prognosis in patients with osteosarcomas. Expressions of MiR-183 and Ezrin mRNA were both examined using quantitative real-time reverse transcriptase-polymerase chain reaction analysis in 68 specimens from patients with osteosarcomas. MiR-183 and Ezrin mRNA expression levels were, respectively, lower and higher in osteosarcoma tissues than those in noncancerous bone tissues significantly (both P < 0.001). Notably, the downregulation of miR-183 was negatively correlated with the upregulation of Ezrin mRNA in osteosarcoma tissues (r = -0.66, P = 0.01). In addition, the combined miR-183 downregulation and Ezrin upregulation (miR-183-low/Ezrin-high) was significantly associated with high tumor grade (P = 0.02), poor response to chemotherapy (P = 0.01), positive metastasis (P = 0.006) and recurrence (P = 0.008). Moreover, miR-183/Ezrin expression and the status of metastasis were both found to be independent prognostic factors for overall survival (P = 0.02 and 0.01, respectively) and disease-free survival (both P = 0.02). Our findings showed that the aberrant expression of miR-183 and its target gene Ezrin may play a crucial role in the development and progression of human osteosarcoma. More interestingly, the dysregulation of miR-183/Ezrin axis may be related to the prediction of aggressiveness and poor prognosis for patients with this lethal disease.

摘要

miR-183(miR-183)通过靶向癌基因 Ezrin 被证明是抑制骨肉瘤迁移和侵袭的肿瘤抑制 miRNA。本研究旨在确定 miR-183 和 Ezrin mRNA 表达的相关性与骨肉瘤患者的临床病理特征和预后的关系。使用定量实时逆转录-聚合酶链反应分析检测 68 例骨肉瘤患者标本中 MiR-183 和 Ezrin mRNA 的表达。与非癌性骨组织相比,骨肉瘤组织中 miR-183 和 Ezrin mRNA 的表达水平均显著降低(均 P < 0.001)。值得注意的是,骨肉瘤组织中 miR-183 的下调与 Ezrin mRNA 的上调呈负相关(r = -0.66,P = 0.01)。此外,miR-183 下调和 Ezrin 上调的联合表达(miR-183-low/Ezrin-high)与高肿瘤分级显著相关(P = 0.02)、对化疗反应不良(P = 0.01)、阳性转移(P = 0.006)和复发(P = 0.008)。此外,miR-183/Ezrin 表达和转移状态均被发现是总生存期(P = 0.02 和 0.01)和无病生存期(均 P = 0.02)的独立预后因素。我们的研究结果表明,miR-183 及其靶基因 Ezrin 的异常表达可能在人类骨肉瘤的发生和发展中起关键作用。更有趣的是,miR-183/Ezrin 轴的失调可能与该致命疾病侵袭性和不良预后的预测有关。

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