miR-15b and miR-21 as Circulating Biomarkers for Diagnosis of Glioma.
miR-15b and miR-21 as Circulating Biomarkers for Diagnosis of Glioma.
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miR-15b和miR-21作为用于诊断神经胶质瘤的循环生物标志物。
DOI：
10.2174/1389202916666150707155610
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发表时间：
2015-10
期刊：
影响因子：
2.6
通讯作者：
Marsigliante S
中科院分区：
文献类型：
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作者：
Ivo D'Urso P;Fernando D'Urso O;Damiano Gianfreda C;Mezzolla V;Storelli C;Marsigliante S
恶性胶质瘤是一种致命性的原发颅内肿瘤。到目前为止，关于非调控基因在胶质瘤中的作用的信息还很少。由于miRNAs在肿瘤发生中的作用是众所周知的，我们开展了一项初步研究，以确定在受胶质瘤影响的患者的血液样本中差异表达的microRNAs作为潜在的生物标志物。我们用基因芯片和实时定量聚合酶链式反应技术研究了30例脑胶质瘤患者和82例脑转移瘤患者血液中miRNAs的表达，这些患者包括：(A)各种神经系统疾病(n=30)，(B)原发性中枢神经系统B淋巴瘤(n=36)和(C)继发性脑转移瘤(n=16)。通过实时定量逆转录聚合酶链式反应(qRT-PCR)，我们发现脑胶质瘤患者血液中两种候选生物标记物miR-15b和miR-21的水平显著升高。ROC分析miR-15b生物标记物水平可用于区分肿瘤患者和非胶质瘤患者。此外，miR15b和miR-21的联合表达分析区分了胶质瘤患者和非胶质瘤患者(90%的敏感性和100%的特异性)。此外，与低级别和间变性胶质瘤相比，miR-16的表达水平降低具有胶质母细胞瘤的特征。总之，这项初步研究表明，通过血液中miR-15b和miR-21标记物的意义来识别疾病状态是可能的，而miR-16可以用于区分胶质母细胞瘤和其他级别的胶质瘤。它们可能被用作非侵入性诊断胶质瘤的生物标记物；进一步的研究是强制性的，以证实我们的初步发现。
Malignant gliomas are lethal primary intracranial tumors. To date, little information on the role of deregulated genes in gliomas have been identified. As the involvement of miRNAs in the carcinogenesis is well known, we carried out a pilot study to identify, as potential biomarkers, differentially expressed microRNAs in blood samples of patients affected by glioma. We studied the miRNAs’ expression, by means of microarray and Real-Time PCR, in 30 blood samples from glioma patients and in 82 blood samples of patients suffering from: (a) various neurological disorders (n=30), (b) primary B-lymphoma of the Central Nervous System (PCNSL, n=36) and (c) secondary brain metastases (n=16). By quantitative real time reverse-transcriptase polymerase chain reaction (qRT-PCR), we identified significantly increased levels of two candidate biomarkers, miR-15b and miR-21, in blood of patients affected by gliomas. ROC analysis of miR-15b biomarker levels allowed to differentiate patients with tumour from patients without glioma. Furthermore, combined expression analyses of miR15b and miR-21 distinguished between patients with and without glioma (90% sensitivity and 100% specificity). In addition, a decrement in the expression levels of miR-16 characterized glioblastomas compared to low grade and anaplastic gliomas. In conclusion, this pilot study suggest that it’s possible to identify the disease state by meaning miR-15b and miR-21 markers in blood, while miR-16 can be used to distinguish glioblastoma from other grade gliomas. They can potentially be used as biomarkers for non-invasive diagnosis of gliomas; further studies are mandatory to confirm our preliminary findings.