Neuronally enriched microvesicle RNAs are differentially expressed in the serums of Parkinson's patients

富含神经元的微泡 RNA 在帕金森病患者血清中存在差异表达

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作者:Morris A Aguilar, Shauna Ebanks, Havell Markus, Mechelle M Lewis, Vishal Midya, Kent Vrana, Xuemei Huang, Molly A Hall, Yuka Imamura Kawasawa

Background

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

Conclusion

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.

Methods

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.

Results

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.

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