Circulating small RNA profiling of patients with alveolar and cystic echinococcosis
Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, supported by serology and clinical and epidemiological data. However, no viability markers that indicate parasite state during infection are available. Extracellular small RNAs (sRNAs) are short non-coding RNAs that can be secreted by cells through association with extracellular vesicles, proteins, or lipoproteins. Circulating sRNAs can show altered expression in pathological states; hence, they are intensively studied as biomarkers of several diseases. Here, we profiled the sRNA transcriptomes in the context of AE and CE to identify novel biomarkers to aid in medical decisions. For this, endogenous and parasitic sRNAs were analysed by sRNA sequencing in sera from disease negative, positive, and treated patients and patients harbouring a non-parasitic lesion. Consequently, 20 differentially expressed sRNAs associated with AE, CE and/or non-parasitic liver lesion were identified. Our results represent an in-depth characterisation of the effect E. multilocularis and E. granulosus s.l. exert on the extracellular sRNA landscape in human infections and provide a set of novel candidate biomarkers for both AE and CE detection. Overall design: small RNA sequencing from serum samples of AE and CE patients was performed. Patients with hepatic non-parasitic lesions (NPL) were also included. The AE set is composed of  Negative,  Positive and Treated patients. The CE set is composed of CE negative patients with no cysts (Negative), CE negative patients with non-parasitic lesion (NPL), CE positive with active cyst (CE1-2), CE positive with transitional cyst (CE3a and CE3b), CE positive with inactive cyst (CE4, CE5) ) that reached inactivation spontaneously and CE positive with albendazole treatment (Treated).