Zhao Jiali, Chen Fengli, Zhou Quan, Pan Wei, Wang Xinhong, Xu Jin, Ni Li, Yang Huilin
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, People's Republic of China; Department of Orthopedics, The Affiliated Huai'an Hospital of Xuzhou Medical College and The Second People's Hospital of Huai'an, Huai'an, People's Republic of China.
Central Laboratory, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, People's Republic of China.
Onco Targets Ther. 2016 Mar 17;9:1589-97. doi: 10.2147/OTT.S102421. eCollection 2016.
The mammalian target of rapamycin (mTOR) has been reported to act as a target gene of microRNA (miR)-99a in various cancer cells and identified as an independent prognostic marker of human osteosarcoma. The aim of this study was to investigate the clinical significance of miR-99a/mTOR axis in human osteosarcoma.
A total of 130 pairs of osteosarcoma and matched noncancerous bone tissues were used to detect the expression levels of miR-99a and mTOR mRNA by quantitative real-time polymerase chain reaction. Then, associations of miR-99a and/or mTOR expression with clinico-pathological features and prognosis of patients with osteosarcoma were statistically analyzed.
The expression levels of miR-99a (tumor vs normal: 2.11±1.03 vs 4.69±1.21, P<0.001) and mTOR mRNA (tumor vs normal: 4.40±1.13 vs 1.74±0.85, P<0.001) in osteosarcoma tissues were, respectively, lower and higher than those in noncancerous bone tissues. The expression levels of miR-99a in osteosarcoma tissues were negatively correlated with those of mTOR mRNA. Additionally, miR-99a-low and/or mTOR-high expression were all significantly associated with advanced surgical stage, positive metastasis and recurrence, and poor response to chemotherapy (all P<0.05). Moreover, patients with osteosarcoma with miR-99a-low and/or mTOR-high expression had shorter overall and disease-free survivals than those in miR-99a-high and/or mTOR-low expression groups. Multivariate Cox analyses showed that miR-99a and/or mTOR expression were all independent prognostic factors of osteosarcoma.
Our data showed the crucial role of miR-99a/mTOR axis in the malignant progression of human osteosarcoma, implying that conjoined expression of miR-99a and mTOR may offer an attractive novel prognostic marker for this disease.
据报道，雷帕霉素哺乳动物靶蛋白（mTOR）在多种癌细胞中作为微小RNA（miR）-99a的靶基因，并被确定为人类骨肉瘤的独立预后标志物。本研究旨在探讨miR-99a/mTOR轴在人类骨肉瘤中的临床意义。
共使用130对骨肉瘤及配对的非癌骨组织，通过定量实时聚合酶链反应检测miR-99a和mTOR mRNA的表达水平。然后，对miR-99a和/或mTOR表达与骨肉瘤患者临床病理特征及预后的相关性进行统计学分析。
骨肉瘤组织中miR-99a（肿瘤组vs正常组：2.11±1.03 vs 4.69±1.21，P<0.001）和mTOR mRNA（肿瘤组vs正常组：4.40±1.13 vs 1.74±0.85，P<0.001）的表达水平分别低于和高于非癌骨组织。骨肉瘤组织中miR-99a的表达水平与mTOR mRNA的表达水平呈负相关。此外，miR-99a低表达和/或mTOR高表达均与手术晚期、阳性转移和复发以及化疗反应差显著相关（均P<0.05）。此外，miR-99a低表达和/或mTOR高表达的骨肉瘤患者的总生存期和无病生存期均短于miR-99a高表达和/或mTOR低表达组。多因素Cox分析表明，miR-99a和/或mTOR表达均为骨肉瘤的独立预后因素。
我们的数据显示了miR-99a/mTOR轴在人类骨肉瘤恶性进展中的关键作用，这意味着miR-99a和mTOR的联合表达可能为该疾病提供一个有吸引力的新预后标志物。
