Multiple Sclerosis Unit, Biodonostia Health Research Institute, San Sebastián 20014, Spain.
Spanish Network of Multiple Sclerosis (REEM), Barcelona 08028, Spain.
Hum Mol Genet. 2020 Dec 18;29(20):3361-3372. doi: 10.1093/hmg/ddaa219.
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, with higher prevalence in women, that leads to neurological disability. The disease course and clinical phenotype are highly variable, and therefore, biomarkers for the diagnosis, classification, monitoring of the disease and treatment assessment are needed. Studies have shown a dysregulation in the coding and non-coding RNAs and proposed some as biomarkers. However, still none of them have reached the clinical practice. Recently, circular RNAs (circRNAs) have emerged as new players in the transcriptome that hold a great potential as biomarkers in several diseases. Leukocytes from 30 MS patients and 20 healthy controls (HCs) were RNA-sequenced to study the linear and circular transcriptome. Differential expression analysis was performed by DESeq, and circRNA candidates were studied in a second cohort (70 MS and 46 HC) by RT-qPCR and in paired samples drawn during the relapse and remission phases (20 patients). Among the differentially expressed circRNAs, 96.1% are upregulated in patients compared with controls, but similar circRNA profiles are found between MS types. The same upregulation trend was observed in females but not in males or in the linear transcriptome. The upregulation of 6 circRNAs was validated, and a change in their expression was found between relapse and remission. The 6 circRNAs showed a good performance to discriminate patients from HC with a combined area under the curve of 0.852. There is global, specific and sex-dependent increase of circRNA expression in MS, and 6 circRNAs are proposed as potential biomarkers.
多发性硬化症（MS）是一种中枢神经系统的慢性自身免疫性疾病，女性发病率较高，可导致神经功能障碍。该疾病的病程和临床表现高度多变，因此需要用于诊断、分类、监测疾病和评估治疗效果的生物标志物。研究表明，编码和非编码 RNA 出现失调，并提出了一些作为生物标志物的 RNA。然而，目前仍没有任何一种 RNA 达到临床应用的水平。最近，环状 RNA（circRNA）作为转录组中的新成员出现，在几种疾病中具有作为生物标志物的巨大潜力。对 30 名 MS 患者和 20 名健康对照者（HC）的白细胞进行 RNA 测序，以研究线性和环状转录组。通过 DESeq 进行差异表达分析，并通过 RT-qPCR 在第二个队列（70 名 MS 和 46 名 HC）中研究 circRNA 候选物，并在复发和缓解阶段（20 名患者）进行配对样本研究。在差异表达的 circRNA 中，96.1%在患者中上调，与对照组相比，但 MS 类型之间存在相似的 circRNA 谱。在女性中观察到相同的上调趋势，但在男性或线性转录组中则没有。验证了 6 个 circRNA 的上调，并发现它们的表达在复发和缓解之间发生变化。这 6 个 circRNA 在区分患者和 HC 方面表现出良好的性能，联合曲线下面积为 0.852。MS 中存在全局、特定和性别依赖的 circRNA 表达上调，提出了 6 个 circRNA 作为潜在的生物标志物。
