Plasma microRNA signature in presymptomatic and symptomatic subjects with C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis.
Plasma microRNA signature in presymptomatic and symptomatic subjects with C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis.
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DOI：
10.1136/jnnp-2020-324647
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
PREV-DEMALS study group
中科院分区：
文献类型：
--
作者：
Kmetzsch V;Anquetil V;Saracino D;Rinaldi D;Camuzat A;Gareau T;Jornea L;Forlani S;Couratier P;Wallon D;Pasquier F;Robil N;de la Grange P;Moszer I;Le Ber I;Colliot O;Becker E;PREV-DEMALS study group
通过评估C9orf72患者和症状前携带者血浆microRNAs （miRNAs）的表达水平，确定9号染色体开放阅读框72基因（C9orf72）相关疾病临床前和临床进展的潜在生物标志物。PREV-DEMALS研究是一项前瞻性研究，包括22名C9orf72患者，45名症状前C9orf72突变携带者和43名对照组。我们使用RNA测序技术评估了所有参与者血浆样本中2576个mirna的表达水平，其中589个高于噪声水平。采用差异表达的mirna在患者、症状前携带者和对照组之间的表达水平构建logistic回归分类器。四种mirna在患者和对照组之间存在差异表达：患者中miR-34a-5p和miR-345-5p过表达，而miR-200c-3p和miR-10a-3p过表达。与健康对照组相比，症状前携带者中MiR-34a-5p也过表达，这表明在C9orf72突变病例中MiR-34a-5p的表达被解除调控。此外，与症状前携带者相比，miR-345-5p在患者中也过表达，这支持了miR-345-5p表达与c9orf72相关疾病进展的相关性。总之，miR-200c-3p和miR-10a-3p低表达可能与疾病的全面爆发有关。4名症状前受试者处于过渡性/前驱期，接近疾病转化，与患者表达水平具有较强的相似性。我们确定了血浆中四个mirna的差异表达特征，这些mirna有可能代表c9orf72相关额颞叶痴呆和肌萎缩性侧索硬化症的进展性生物标志物。这项研究表明，在神经退行性疾病的进展过程中，mirna的失调是动态改变的，甚至在临床发病前很久就可以检测到。NCT02590276。
To identify potential biomarkers of preclinical and clinical progression in chromosome 9 open reading frame 72 gene (C9orf72)-associated disease by assessing the expression levels of plasma microRNAs (miRNAs) in C9orf72 patients and presymptomatic carriers. The PREV-DEMALS study is a prospective study including 22 C9orf72 patients, 45 presymptomatic C9orf72 mutation carriers and 43 controls. We assessed the expression levels of 2576 miRNAs, among which 589 were above noise level, in plasma samples of all participants using RNA sequencing. The expression levels of the differentially expressed miRNAs between patients, presymptomatic carriers and controls were further used to build logistic regression classifiers. Four miRNAs were differentially expressed between patients and controls: miR-34a-5p and miR-345-5p were overexpressed, while miR-200c-3p and miR-10a-3p were underexpressed in patients. MiR-34a-5p was also overexpressed in presymptomatic carriers compared with healthy controls, suggesting that miR-34a-5p expression is deregulated in cases with C9orf72 mutation. Moreover, miR-345-5p was also overexpressed in patients compared with presymptomatic carriers, which supports the correlation of miR-345-5p expression with the progression of C9orf72-associated disease. Together, miR-200c-3p and miR-10a-3p underexpression might be associated with full-blown disease. Four presymptomatic subjects in transitional/prodromal stage, close to the disease conversion, exhibited a stronger similarity with the expression levels of patients. We identified a signature of four miRNAs differentially expressed in plasma between clinical conditions that have potential to represent progression biomarkers for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis. This study suggests that dysregulation of miRNAs is dynamically altered throughout neurodegenerative diseases progression, and can be detectable even long before clinical onset. NCT02590276.
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影响因子：
4.5
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影响因子：
3.7
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通讯作者：
FTLDc study group