循环微小RNA作为高级别胶质瘤的诊断和预后生物标志物
Circulating miRNAs as Diagnostic and Prognostic Biomarkers in High-Grade Gliomas.
作者信息
Wu Jianing, Al-Zahrani Abdulrahman, Beylerli Ozal, Sufianov Rinat, Talybov Rustam, Meshcheryakova Svetlana, Sufianova Galina, Gareev Ilgiz, Sufianov Albert
机构信息
Department of Neurosurgery, Shenzhen University General Hospital, Guangdong, China.
Department of Neurosurgery, Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
出版信息
Front Oncol. 2022 May 12;12:898537. doi: 10.3389/fonc.2022.898537. eCollection 2022.
OBJECTIVES
miR-181a/b and miR-410 downregulation and miR-155 upregulation has been shown to play important roles in the oncogenesis and progression of gliomas including high-grade gliomas. However, the potential role of plasma miR-181a/b, miR-410 and miR-155 in the diagnosis and prognosis of high-grade gliomas remains poorly known.
METHODS
We retrieved published articles from the PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science database and obtained different sets of data on microRNAs (miRNAs) expression profiling in glioma and highlighted the most frequently dysregulated miRNAs and their gene-targets (PDCD4, WNT5A, MET, and EGFR) in high-grade gliomas. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was carried out to measure the pre- and postoperative plasma levels of miR-181a/b, miR-410 and miR-155 in 114 Grade 3-4 glioma patients, 77 Grade 1-2 glioma patients and 85 healthy volunteers as control group. The diagnostic and prognostic value of circulating miR-181a/b, miR-410 and miR-155 as biomarker was estimated by the Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) and Kaplan-Meier analysis.
RESULTS
We found a plasma miRNA signature including three downexpressed miRNAs and one overexpressed (miR-181a, miR-181b and miR-410; miR-155) in high-grade glioma patients in comparison with low-grade glioma patients control group. The ROC curve AUC of these four circulating miRNAs were ≥ 0.75 for high-grade glioma patients in before and after surgery. Higher circulating miR-155 and lower miR-181a/b and miR-410 expression is associated with clinical data, clinic pathological variables, worse overall survival (OS) of patients and negative correlated with potential gene-targets expression. Moreover, Kaplan-Meier analysis showed that miR-181a/b, miR-410 and miR-155 were independent predictors of OS in high-grade glioma patients.
CONCLUSIONS
Our data, for the first time, demonstrated that circulating miR-181a/b, miR-410 and miR-155 could be a useful diagnostic and prognostic non-invasive biomarkers in high-grade gliomas.
目的
已有研究表明，miR-181a/b 和 miR-410 的下调以及 miR-155 的上调在包括高级别胶质瘤在内的胶质瘤的发生和发展中起重要作用。然而，血浆 miR-181a/b、miR-410 和 miR-155 在高级别胶质瘤诊断和预后中的潜在作用仍鲜为人知。
方法
我们从 PubMed、Cochrane 对照试验中央注册库和 Web of Science 数据库中检索已发表的文章，并获取了关于胶质瘤中 microRNA（miRNA）表达谱的不同数据集，并重点关注了高级别胶质瘤中最常失调的 miRNAs 及其基因靶点（PDCD4、WNT5A、MET 和 EGFR）。采用定量逆转录聚合酶链反应（qRT-PCR）检测 114 例 3-4 级胶质瘤患者、77 例 1-2 级胶质瘤患者和 85 名健康志愿者作为对照组术前和术后血浆中 miR-181a/b、miR-410 和 miR-155 的水平。通过受试者工作特征（ROC）曲线、曲线下面积（AUC）和 Kaplan-Meier 分析评估循环 miR-181a/b、miR-410 和 miR-155 作为生物标志物的诊断和预后价值。
结果
我们发现，与低级别胶质瘤患者对照组相比，高级别胶质瘤患者存在一种血浆 miRNA 特征，包括三种表达下调的 miRNA 和一种表达上调的 miRNA（miR-181a、miR-181b 和 miR-410；miR-155）。这四种循环 miRNA 的 ROC 曲线 AUC 在高级别胶质瘤患者术前和术后均≥0.75。循环 miR-155 水平较高以及 miR-181a/b 和 miR-410 表达较低与临床数据、临床病理变量、患者较差的总生存期（OS）相关，且与潜在基因靶点的表达呈负相关。此外，Kaplan-Meier 分析表明，miR-181a/b、miR-410 和 miR-155 是高级别胶质瘤患者 OS 的独立预测指标。
结论
我们的数据首次证明，循环 miR-181a/b、miR-410 和 miR-155 可能是高级别胶质瘤中有用的诊断和预后非侵入性生物标志物。
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