Circulating microRNA signatures for echinococcosis.

BACKGROUND: Echinococcosis, a serious zoonotic parasitic disease caused by tapeworms of the genus Echinococcus, is clinically characterized by a long latent period of up to 10 years. An accurate diagnosis is critical for the efficient management and treatment of patients. The aim of this study was to identify robust diagnostic signatures for echinococcosis. METHODS: Using co-immunoprecipitation and RNA sequencing (RNA-seq), we comparatively profiled the Argonaute 2-binding microRNAs (abmiRNAs) in hepatocytes of Echinococcus multilocularis-infected mice. Using receiver operating characteristic curve (ROC) analysis, we established quantitative PCR (qPCR) assays based on circulating liver-specific abmiRNAs and their combinations, and further validated these assays using blinded serum samples from infected mice and patients. RESULTS: Three abmiRNAs were identified as being predominantly expressed in the liver: miR-192-5p, miR-122-5p and miR-21a-5p. While these three abmiRNAs are upregulated in liver cancer and hepatitis virus infections, we found that all circulating abmiRNAs were significantly and gradually downregulated as the Emultilocularis infection progressed; however, they were rapidly upregulated following anthelmintic treatment. The qPCR assays targeting these circulating abmiRNAs and their combinations showed high sensitivity and specificity. Individual circulating abmiRNAs and their combinations accurately distinguished infections in both mice (n = 50) and humans (n = 117), with the combination of miR-192-5p and miR-122-5p being particularly effective in distinguishing infections. This combination was also sensitive to anthelmintic treatment. CONCLUSIONS: These results suggest that circulating miR-192-5p and miR-122-5p are serum signatures for the diagnosis and prognostic management of echinococcosis.