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bioRxiv · 10.1101/2022.05.04.490596

Plasma miRNA-214 is a predictive candidate biomarker of progression speed in patients with ALS

Noh, M.-Y.·Kwon, M.-S.·Oh, K.-w.·Nahm, M.·Park, J.·Kim, Y.-E.·Jin, H. K.·Bae, J.-s.·Ki, C.-S.·Kim, S. H.
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Abstract

This study was designed to develop and validate a reliable biomarker to predict the progression speed reflecting immune function of amyotrophic lateral sclerosis (ALS). After establishing the induced microglia model (iMGs) derived from peripheral blood monocytes, comparative studies to find factors related to phagocytic differences between iMGs of patients with rapidly progressive ALS [ALS(R)-iMGs, n = 15] and those of patients with slowly progressive ALS [ALS(S)-iMGs, n = 14] were conducted in the discovery cohort. To validate discovered candidate and whether it could be used as a reliable biomarker predicting the progression speed of ALS, we recruited 132 patients with ALS and 30 age-matched healthy controls as the validation cohort. ALS(R)-iMGs showed impaired phagocytic function. Transcriptomic analysis revealed that the perturbed phagocytosis in ALS(R)-iMGs was related to the decreased expression of NCKAP1 (NCK-associated protein 1) and NCKAP1 overexpression rescued the impaired phagocytic function. miRNA-214-3p targeting NCKAP1 in ALS-iMGs was correlated with progression speed in the discovery cohort. The validation cohort revealed that plasma miRNA-214-3p levels were significantly increased in ALS patients (p < 0.0001, AUC = 0.839), correlated with disease progression speed (p = 0.0005), and distinguished the rapidly progressive subgroup (Q1) from the slowly progressive (Q4, p = 0.029), respectively. Plasma miRNA-214-3p can predict the progression speed in ALS. Plasma miRNA-214-3p could be used as a simple and easily accessible biomarker for predicting the future progression speed related to phagocytic dysfunction in ALS patients.

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Noh, M.-Y., Kwon, M.-S., Oh, K.-w., Nahm, M., Park, J., Kim, Y.-E., Jin, H. K., Bae, J.-s., Ki, C.-S., Kim, S. H.. 2022-05-04. Plasma miRNA-214 is a predictive candidate biomarker of progression speed in patients with ALS. https://doi.org/10.1101/2022.05.04.490596

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