Serum aca-mir-146a is a potential biomarker for early diagnosis of Angiostrongylus cantonensis infection.

ABSTRACT

Infection with Angiostrongylus cantonensis can cause eosinophilic meningoencephalitis, but it lacks an effective early diagnostic tool for the disease. Recently, growing number of serum microRNAs (miRNAs) were investigated to serve as potentially noninvasive biomarkers for various diseases. However, it is unclear if the molecule can considered a biomarker for diagnosing the infection of A. cantonensis. Here, we attempted to identify potential A. cantonensis-derived miRNAs for the early diagnosis of angiostrongyliasis. Through Solexa deep sequencing and GO "biological process" classifications, we found that there were 18 miRNAs of significantly differential expression in the fourth-stage larvae (L4) larva of A. cantonensis when compared with the third-stage larvae (L3) larva of A. cantonensis. Among the 18 miRNAs, the sequences of 6 miRNAs, including aca-miR-29a, aca-miR-124, aca-miR-125a, aca-miR-146a, aca-miR-101, and aca-miR-185, were different from human- and mouse-derived miRNAs (both are the nonpermissive hosts of A. cantonensis). The expression patterns of the six A. cantonensis-derived miRNAs in serum were investigated by polymerase chain reaction on the A. cantonensis-infected mice and their controls. We found that aca-miR-146a had a significantly higher expression level in every experimental positive group, which suggested that this miRNA might be useful for early diagnosis. Receiver operating characteristic (ROC) curve analysis showed that aca-miR-146a was an effective biomarker for discriminating A. cantonensis-infected mice from healthy control cases, with an area under the ROC curve (AUC) of 0.90. Its diagnostic accuracy was assessed on patients (n = 30) and healthy controls (n = 30), and the sensitivity and specificity reached 83 and 86.7 %, respectively. Our study revealed that aca-mir-146a in serum is an effective biomarker to track infection of A. cantonensis.