Aguilar Morris A, Ebanks Shauna, Markus Havell, Lewis Mechelle M, Midya Vishal, Vrana Kent, Huang Xuemei, Hall Molly A, Kawasawa Yuka Imamura
Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA, United States.
Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, United States.
Front Neurosci. 2023 Jul 6;17:1145923. doi: 10.3389/fnins.2023.1145923. eCollection 2023.
Circulating small RNAs (smRNAs) originate from diverse tissues and organs. Previous studies investigating smRNAs as potential biomarkers for Parkinson's disease (PD) have yielded inconsistent results. We investigated whether smRNA profiles from neuronally-enriched serum exosomes and microvesicles are altered in PD patients and discriminate PD subjects from controls.
Demographic, clinical, and serum samples were obtained from 60 PD subjects and 40 age- and sex-matched controls. Exosomes and microvesicles were extracted and isolated using a validated neuronal membrane marker (CD171). Sequencing and bioinformatics analyses were used to identify differentially expressed smRNAs in PD and control samples. SmRNAs also were tested for association with clinical metrics. Logistic regression and random forest classification models evaluated the discriminative value of the smRNAs.
In serum CD171 enriched exosomes and microvesicles, a panel of 29 smRNAs was expressed differentially between PD and controls (false discovery rate (FDR) < 0.05). Among the smRNAs, 23 were upregulated and 6 were downregulated in PD patients. Pathway analysis revealed links to cellular proliferation regulation and signaling. Least absolute shrinkage and selection operator adjusted for the multicollinearity of these smRNAs and association tests to clinical parameters via linear regression did not yield significant results. Univariate logistic regression models showed that four smRNAs achieved an AUC ≥ 0.74 to discriminate PD subjects from controls. The random forest model had an AUC of 0.942 for the 29 smRNA panel.
CD171-enriched exosomes and microvesicles contain the differential expression of smRNAs between PD and controls. Future studies are warranted to follow up on the findings and understand the scientific and clinical relevance.
循环小RNA（smRNA）起源于多种组织和器官。先前关于将smRNA作为帕金森病（PD）潜在生物标志物的研究结果并不一致。我们研究了神经元富集的血清外泌体和微泡中的smRNA谱在PD患者中是否发生改变，以及能否区分PD患者与对照组。
收集60例PD患者和40例年龄及性别匹配的对照者的人口统计学、临床和血清样本。使用经过验证的神经元膜标记物（CD171）提取和分离外泌体和微泡。通过测序和生物信息学分析确定PD样本和对照样本中差异表达的smRNA。还测试了smRNA与临床指标的关联。逻辑回归和随机森林分类模型评估了smRNA的判别价值。
在血清CD171富集的外泌体和微泡中，29种smRNA在PD患者和对照组之间存在差异表达（错误发现率（FDR）<0.05）。在这些smRNA中，PD患者中有23种上调，6种下调。通路分析揭示了与细胞增殖调节和信号传导的联系。通过线性回归对这些smRNA的多重共线性进行调整的最小绝对收缩和选择算子以及与临床参数的关联测试未得出显著结果。单变量逻辑回归模型显示，四种smRNA区分PD患者与对照组的曲线下面积（AUC）≥0.74。29种smRNA组合的随机森林模型的AUC为0.942。
CD171富集的外泌体和微泡包含PD患者与对照组之间smRNA的差异表达。有必要开展进一步研究以跟进这些发现并了解其科学和临床意义。
