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脑脊液miRNA谱作为前庭神经鞘瘤潜在液体活检的研究

Cerebrospinal Fluid miRNA Profiling as a Potential Liquid Biopsy for Vestibular Schwannomas.

基础研究耳科IF 4.2Q1

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中文摘要

背景/目的: 本研究旨在识别前庭神经鞘瘤患者脑脊液中特征性的miRNA表达谱,并评估其用于肿瘤评估的潜力。方法:在这项前瞻性研究中,从一家三级学术中心接受前庭神经鞘瘤手术的患者中收集了17份脑脊液及相应的肿瘤样本(7例小肿瘤-SVS和10例大肿瘤-LVS)。使用高通量RNA测序(NovaSeq 6000 Illumina)分析miRNA表达。对数据进行标准化,并对前庭神经鞘瘤患者与公共健康供体数据集之间的miRNA表达排名进行比较分析。通过KEGG通路富集分析探讨功能意义。结果:在所有来自前庭神经鞘瘤患者的脑脊液样本中共鉴定出1633个miRNA。与健康供体比较显示中等程度的排名相关性(ρ = 0.39),特定分子如hsa-miR-766-3p和hsa-miR-182-5p存在显著变化。仅发现6个miRNA在脑脊液与肿瘤组织之间具有相关性,而16个呈负相关。肿瘤大小与脑脊液miRNA谱之间未发现统计学相关性。KEGG分析突出了富集的通路,包括神经营养因子信号传导和黏着斑。结论:本研究结果支持基于miRNA的脑脊液液体活检用于前庭神经鞘瘤评估的可行性。然而,在肿瘤组织中进行的miRNA表达谱分析结果不能直接转移到脑脊液样本分析中。需要进一步研究来解释这一现象,并在脑脊液液体活检标本中寻找可靠的前庭神经鞘瘤进展miRNA标志物。

英文摘要

Background/Objectives: This study aimed to identify a characteristic miRNA expression profile in the CSF of patients diagnosed with vestibular schwannoma and evaluate its potential for tumor assessment. Methods: In this prospective study, 17 CSF and corresponding tumor samples (seven small tumors-SVS and 10 large tumors-LVS) were collected from patients operated on for VS in a Tertiary Academic Center. The miRNA expression was analyzed using high-throughput RNA sequencing (NovaSeq 6000 Illumina). Data were normalized, and a comparative analysis of miRNA expression rankings was performed between VS patients and a public healthy donor dataset. Functional implications were explored using KEGG pathway enrichment analysis. Results: A total of 1633 miRNAs were identified in all CSF samples derived from VS patients. Comparison with healthy donors revealed a moderate ranking correlation (ρ = 0.39), with significant shifts for specific molecules like hsa-miR-766-3p and hsa-miR-182-5p. Only six miRNAs were found to correlate between CSF and tumor tissue, while 16 exhibited a negative correlation. No statistical correlation was found between tumor size and the CSF miRNA profile. KEGG analysis highlighted enriched pathways, including neurotrophin signaling and focal adhesion. Conclusions: The results of our study support the feasibility of miRNA-based CSF liquid biopsy for VS assessment. However, the results of miRNA expression profiling conducted in tumor tissue cannot be directly transferred into CSF sample analyses. Further studies are warranted to explain this phenomenon and to search for reliable miRNA markers of VS progression in the CSF liquid biopsy specimens.