Orlandi Riccardo, Torresan Leopoldo, Gobbin Francesca, Orlandi Elisa, Gomez Lira Macarena, Gajofatto Alberto
Department of Neurological Sciences, Biomedicine and Movement Sciences, University of Verona, Piazzale Ludovico Antonio Scuro 9, 37134 Verona, Italy.
Int J Mol Sci. 2025 Sep 4;26(17):8597. doi: 10.3390/ijms26178597.
In recent years, research has focused on biomarkers as key tools to predict clinical outcomes and guide therapeutic decisions in Multiple Sclerosis (MS). MicroRNAs (miRs)-small non-coding RNA molecules that regulate gene expression at the post-transcriptional level-have emerged as promising biomarkers in MS due to their accessibility in biological fluids. This study investigates the role of specific serum miRs mainly involved in immune response regulation as potential prognostic biomarkers in MS, focusing on young patients with recent diagnosis. The study had a prospective design, involving a cohort of patients followed in the Hub and Spoke MS network of Verona province. Fifty-one patients (33F) aged 18-40 years with recent MS diagnosis (≤2 years; 45 relapsing-remitting, 6 primary progressive) were consecutively enrolled. At baseline, serum samples were collected for miR analysis alongside clinical-demographic and MRI data, including T2 lesion volume, normalized brain volume (NBV), gray matter volume, white matter volume (WMV) calculated at baseline and annual percentage brain volume change (PBVC) and occurrence of new T2 or gadolinium-enhancing (Gd+) lesions on follow-up scans. Candidate miRs were chosen based on their potential biological role in MS pathogenesis reported in the literature. miRs assays were done using real-time PCR and expressed as a ratio relative to a normalizer (i.e., miR-425-5p). Levels of miR-34a-5p were significantly higher in patients with Gd+ lesions ( < 0.001) and correlated to lower NBV (rho = -0.454, = 0.001) and WMV (rho = -0.494, < 0.001). Conversely, miR-140-5p exhibited a protective effect against occurrence of new T2 or Gd+ lesions over time (HR 0.43; IC 95% 0.19-0.99; = 0.048). Additionally, miR-30b-5p correlated directly with PBVC (adjusted rho = -0.646; < 0.001). These findings support the potential of serum miR-34a-5p, miR-140-5p, and miR-30b-5p as markers of disease activity and progression in patients with recently diagnosed MS.
近年来，研究聚焦于生物标志物，将其作为预测多发性硬化症（MS）临床结局及指导治疗决策的关键工具。微小RNA（miRs）是一类在转录后水平调控基因表达的小型非编码RNA分子，因其在生物体液中易于获取，已成为MS中有前景的生物标志物。本研究调查了主要参与免疫反应调节的特定血清miRs作为MS潜在预后生物标志物的作用，重点关注近期诊断的年轻患者。该研究采用前瞻性设计，纳入了维罗纳省中枢与分支MS网络中随访的一组患者。连续纳入了51例年龄在18至40岁之间、近期诊断为MS（≤2年；45例复发缓解型，6例原发进展型）的患者。在基线时，采集血清样本进行miR分析，同时收集临床人口统计学和MRI数据，包括T2病变体积、正常脑体积（NBV）、灰质体积、基线时计算的白质体积（WMV）以及年度脑体积变化百分比（PBVC），还有随访扫描中新发T2或钆增强（Gd +）病变的发生情况。候选miRs是根据文献报道的它们在MS发病机制中的潜在生物学作用来选择的。使用实时PCR进行miR检测，并表示为相对于标准化物（即miR - 425 - 5p）的比值。Gd +病变患者的miR - 34a - 5p水平显著更高（<0.001），且与较低的NBV（rho = -0.454，= 0.001）和WMV（rho = -0.494，<0.001）相关。相反，随着时间推移，miR - 140 - 5p对新发T2或Gd +病变的发生具有保护作用（HR 0.43；95%置信区间0.19 - 0.99；= 0.048）。此外，miR - 30b - 5p与PBVC直接相关（校正rho = -0.646；<0.001）。这些发现支持血清miR - 34a - 5p、miR - 140 - 5p和miR - 30b - 5p作为近期诊断MS患者疾病活动和进展标志物的潜力。
