Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma.
Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma.
复制标题
DOI：
10.18632/oncotarget.16498
复制
发表时间：
2017-05-16
期刊：
影响因子：
--
通讯作者：
Ozaki T
中科院分区：
文献类型：
--
作者：
Fujiwara T;Uotani K;Yoshida A;Morita T;Nezu Y;Kobayashi E;Yoshida A;Uehara T;Omori T;Sugiu K;Komatsubara T;Takeda K;Kunisada T;Kawamura M;Kawai A;Ochiya T;Ozaki T
新出现的证据表明，体液循环中的microRNAs （miRNAs）对恶性疾病患者具有新的诊断和预后意义。缺乏有用的生物标志物是骨和软组织肉瘤的一个关键问题；因此，我们研究了循环miRNA特征及其在骨肉瘤中的临床意义。使用从骨肉瘤患者和对照组的发现队列中收集的患者血清和细胞培养基进行全球miRNA分析。通过体外和体内模型以及验证患者队列评估骨肉瘤细胞中检测到的miRNA分泌和血清miRNA水平的临床相关性。与对照组相比，发现筛选鉴定出236个在骨肉瘤患者中高表达的血清mirna，其中8个在细胞培养基中也被鉴定出来。在骨肉瘤细胞中发现miR-17-5p和miR-25-3p的表达水平上调，并且它们在肿瘤来源的外泌体中大量分泌到培养基中。验证队列中骨肉瘤患者血清miR-25-3p水平明显高于对照组，与血清碱性磷酸酶相比具有良好的敏感性和特异性。此外，在体内模型和患者中，诊断时血清miR-25-3p水平与患者预后相关，反映肿瘤负荷；这些相关性比血清碱性磷酸酶的相关性更敏感。基于血清的循环miR-25-3p可作为骨肉瘤患者肿瘤监测和预后预测的非侵入性血液生物标志物。
Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.