Signatures of circulating microRNA in four sarcoma subtypes
Signatures of circulating microRNA in four sarcoma subtypes
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DOI：
10.7150/jca.34723
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Ostrowski, Jerzy
中科院分区：
文献类型：
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作者：
Kosela-Paterczyk, Hanna;Paziewska, Agnieszka;Ostrowski, Jerzy
背景：肉瘤是一种罕见的间叶性恶性肿瘤。具有很高诊断价值的循环生物标志物的发现可以补充对这一异质性肿瘤的诊断。本研究的目的是确定四组常见的骨和软组织肉瘤中循环miRNA(c-miRNAs)的分布情况。方法：确诊时采集86例患者的血液样本：36例局部晚期/不能切除/转移性胃肠道间质瘤(GIST)接受伊马替尼一线治疗；16例局部晚期骨肉瘤(OS)；26例局部晚期滑膜肉瘤(SS)；8例局部晚期尤文肉瘤(ES)。此外，还采集了30名健康对照的样本。用miRCURY RNA分离试剂盒分离c-miRNAs，然后制备c-miRNAs文库，并在Ion Proton平台上测序。结果：配对比较发现156个独特的c-miRNAs(调整后的P值和0.05)在对照组和患者之间存在显著的调节异常；其中，24、36、42和99个不同的对照组分别来自治疗前的OS、SS、ES和GIST。在至少三种肉瘤类型中，通常有10个c-miRNAs发生改变。受试者工作特征曲线和曲线下面积(ROC-AUC)分析表明，4-miRNA诊断分类器能够区分ES、GIST、OS和SS，其AUC-ROC值分别为1、0.97、0.95和0.94。结论：在4种不同肉瘤亚型的患者血清中发现了异常的miRNA表达特征。肉瘤患者和健康志愿者之间miRNA表达谱的差异表明miRNAs可能在肉瘤的发展中发挥作用。
Background: Sarcomas are rare malignant tumors of mesenchymal origin. The discovery of circulating biomarkers with high diagnostic value could supplement diagnosis of this heterogenous group of tumors. The aim of this study was to identify the profiles of circulating miRNA (c-miRNAs) in four groups of common bone and soft tissue sarcomas.Methods: At the time of diagnosis, blood samples were collected from 86 patients: 36 with locally advanced/unresectable/metastatic gastrointestinal stromal tumor (GIST) who received first-line treatment with imatinib; 16 with locally advanced osteosarcoma (OS); 26 with locally advanced synovial sarcoma (SS); and eight with locally advanced Ewing sarcoma (ES). In addition, samples were collected from 30 healthy controls. C-miRNAs were isolated using a miRCURY RNA Isolation Kit, followed by preparation of cDNA libraries and sequencing on the Ion Proton platform.Results: Pair-wise comparisons identified 156 unique c-miRNAs (adjusted P-value < 0.05) showing significant dysregulation between controls and patients; of these, 24, 36, 42, and 99 differentiated controls from pretherapeutic OS, SS, ES, and GIST, respectively. Ten c-miRNAs were commonly altered in at least three sarcoma types. Receiver operating characteristic curves and area under the curve (ROC-AUC) analyses revealed that a four-miRNA diagnostic classifier was able to differentiate controls from ES, GIST, OS, and SS, with AUC-ROC values of 1, 0.97, 0.95, and 0.94, respectively.Conclusions: Aberrant miRNA expression signatures were identified in serum from patients with four different sarcoma subtypes. Differences in miRNA expression profiles between sarcoma patients and healthy volunteers suggest that miRNAs may play a role in sarcoma development.