Altered exosomal miRNA profiles in patients with paraneoplastic cerebellar degeneration.

IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Annals of Clinical and Translational Neurology Pub Date : 2024-10-29 DOI:10.1002/acn3.52232
Eirik Tveit Solheim, Liv Cecilie Vestrheim Thomsen, Line Bjørge, Shamundeeswari Anandan, Elise Peter, Virginie Desestret, Cecilie Totland, Christian A Vedeler
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Abstract

Objective: Patients with ovarian cancer (OC) may develop anti-Yo-associated paraneoplastic cerebellar degeneration (PCD)-a cerebellar ataxia associated with tumor-induced autoimmunity against CDR2 and CDR2L proteins. Dysregulation of circulating exosomal microRNAs (miRNAs) occur in OC. Here, we investigated whether PCD is associated with changes in the exosomal miRNA profiles of OC patients.

Methods: Serum exosomes were isolated from patients with OC (n = 15), patients with OC and anti-Yo-associated PCD (n = 14) and healthy controls (HC, n = 15). Small RNA sequencing was used to identify differentially expressed miRNAs. Receiver operating characteristic curves were used to evaluate biomarker sensitivity and specificity, and miRNA target prediction analysis was employed to elucidate gene targets.

Results: OC patients with PCD exhibited a distinct exosomal miRNA expression profile. We detected 103 differentially expressed exosomal miRNAs in PCD patients compared to OC patients without PCD and 139 differentially expressed exosomal miRNAs compared to controls. Particularly miR-486-5p, miR-4732-5p, miR-98-5p and miR-21-5p exhibited notable sensitivity and specificity for discriminating PCD patients from both OC patients without PCD and healthy controls. miRNA target prediction showed that several of the differentially expressed miRNAs in PCD patients targeted the CDR2 and CDR2L genes.

Interpretation: Our results demonstrate that OC patients with anti-Yo-associated PCD exhibit a distinct exosomal miRNA profile compared to OC patients without PCD. Several of the differentially expressed exosomal miRNAs in PCD patients showed diagnostic potential and may hold relevance for understanding the pathogenesis of PCD.

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副肿瘤性小脑变性患者的外泌体miRNA谱发生变化。
目的:卵巢癌(OC)患者可能会出现抗-Yo相关的副肿瘤性小脑变性(PCD)--一种与肿瘤诱导的针对CDR2和CDR2L蛋白的自身免疫相关的小脑共济失调。OC中会出现循环外泌体微RNA(miRNA)失调。在此,我们研究了PCD是否与OC患者外泌体miRNA谱的变化有关:方法:从OC患者(n = 15)、OC和抗-Yo相关PCD患者(n = 14)以及健康对照组(HC,n = 15)分离血清外泌体。利用小 RNA 测序鉴定差异表达的 miRNA。利用接收者操作特征曲线评估生物标志物的敏感性和特异性,并采用miRNA靶标预测分析来阐明基因靶标:结果:患有PCD的OC患者表现出独特的外泌体miRNA表达谱。与未患 PCD 的 OC 患者相比,我们在 PCD 患者体内检测到 103 个表达不同的外泌体 miRNA;与对照组相比,我们检测到 139 个表达不同的外泌体 miRNA。特别是 miR-486-5p、miR-4732-5p、miR-98-5p 和 miR-21-5p 在区分 PCD 患者与非 PCD OC 患者和健康对照组方面表现出显著的敏感性和特异性:我们的研究结果表明,与不伴有PCD的OC患者相比,伴有抗-Yo相关PCD的OC患者表现出独特的外泌体miRNA谱。PCD患者体内表达不同的几种外泌体miRNA具有诊断潜力,可能与了解PCD的发病机制有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)
CiteScore
9.10
自引率
1.90%
发文量
218
审稿时长
8 weeks
期刊介绍: Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.
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