Khatami Nasrin, Caraus Iurie, Rahaman Mahamuda, Nepotchatykh Evguenia, Elbakry Mohamed, Elremaly Wesam, Franco Anita, Beauséjour Marie, Laberge Anne-Marie, Parent Stefan, Labelle Hubert, Aubin Carl-Éric, Lachaine Jean, Moreau Alain
Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, room 2.17.027, 3175 Cote-Ste-Catherine Road, Montreal, QC, H3T 1C5, Canada.
Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Université de Montréal, Montreal, QC, Canada.
Sci Rep. 2025 Feb 12;15(1):5305. doi: 10.1038/s41598-025-88985-3.
Adolescent Idiopathic Scoliosis (AIS) is the most common orthopedic condition requiring surgery, affecting 4% of adolescents. There is currently no proven method or prognostic test to identify symptomatic patients at risk of developing severe scoliosis who could benefit from growth-guided devices or minimally invasive non-fusion instrumentation surgeries. These innovative treatments must be performed at an early disease stage in younger patients to benefit from their growth potential. In this prospective cross-sectional study, we investigated the clinical utility of circulating microRNAs (miRNAs), an important class of small non-coding RNA, as biomarkers to predict the risk of developing severe scoliosis in AIS. Blood samples and clinical data were collected from 116 AIS patients who were followed until skeletal maturity and stratified according to their clinical outcome. Genome-wide expression profiling of miRNAs was performed with plasma obtained at the time of diagnosis of AIS (mean age of 13.3 ± 1.7 years with a mean Cobb angle of 24.4° ± 12.4°). This approach led to the identification of 15 circulating miRNAs that are upregulated in AIS patients who developed a severe scoliosis (Cobb angle ≥ 45°) at skeletal maturity compared to moderate and mild scoliosis groups (Cobb angle between 25°-44° and < 25° respectively). After optimization and the application of Random Forest Models a panel of six miRNAs (miR-1-3p, miR-19a-3p, miR-19b-3p, miR-133b, miR-143-3p, and miR-148b-3p) out of 15 led us to develop an algorithm predicting the risk of developing a severe scoliosis with great accuracy (100%), sensitivity (100%) and specificity (100%). Having a scoliosis predictive bioassay and decision-making tools to predict curve progression in order to find the best treatment plan will undoubtedly transform the orthopedic care system in the field of pediatric scoliosis by integrating innovative precision medicine approaches. In addition, investigation of genes targeted by these miRNAs could fill our gaps in our understanding of AIS pathogenesis and reveal new actionable targets.
青少年特发性脊柱侧弯（AIS）是最常见的需要手术治疗的骨科疾病，影响4%的青少年。目前尚无经证实的方法或预后测试来识别有发展为严重脊柱侧弯风险的有症状患者，这些患者可能从生长引导装置或微创非融合器械手术中获益。这些创新治疗必须在年轻患者的疾病早期进行，以利用其生长潜力。在这项前瞻性横断面研究中，我们调查了循环微小RNA（miRNA）作为生物标志物预测AIS患者发生严重脊柱侧弯风险的临床效用，miRNA是一类重要的小型非编码RNA。从116例AIS患者中采集血样和临床数据，对这些患者进行随访直至骨骼成熟，并根据其临床结果进行分层。在AIS诊断时（平均年龄13.3±1.7岁，平均Cobb角24.4°±12.4°）采集血浆，进行miRNA的全基因组表达谱分析。该方法导致识别出15种循环miRNA，与中度和轻度脊柱侧弯组（Cobb角分别在25°-44°和<25°之间）相比，在骨骼成熟时发展为严重脊柱侧弯（Cobb角≥45°）的AIS患者中这些miRNA上调。经过优化并应用随机森林模型后，15种miRNA中的6种（miR-1-3p、miR-19a-3p、miR-19b-3p、miR-133b、miR-143-3p和miR-148b-3p）使我们开发出一种算法，能够以极高的准确性（100%）、敏感性（100%）和特异性（100%）预测发生严重脊柱侧弯的风险。拥有一种脊柱侧弯预测生物测定法和决策工具来预测曲线进展，以便找到最佳治疗方案，无疑将通过整合创新的精准医学方法改变小儿脊柱侧弯领域的骨科护理系统。此外，对这些miRNA靶向基因的研究可以填补我们对AIS发病机制理解上的空白，并揭示新的可操作靶点。
