Sonobiopsy for enrichment of circulating microRNAs in glioma patients

Sonobiopsy is a promising new technique that employs focused ultrasound (FUS) to noninvasively enrich brain tumor-derived biomarkers from spatially targeted brain location into the bloodstream. Building upon our recent first-in-human sonobiopsy trial demonstrating enrichment of circulating tumor DNA (ctDNA), here we investigated whether sonobiopsy can enhance the release and detection of tumor-derived microRNAs (miRNAs).

Eleven patients with glioma underwent FUS sonication immediately prior to surgical resection. Peripheral blood samples were collected 5 min before and 5, 10, and 30 min after sonication. Plasma and brain tissue miRNA levels were quantified through small RNA sequencing and compared among different time points.

Plasma miRNAs that were below the detection threshold [reads per million (RPM) <10] showed significant enrichment at all post-FUS time points across all patients, with a maximal increase of 8.7-fold at 30 min. In contrast, miRNAs above the detection threshold (RPM ≥10) exhibited no significant change following FUS. Among the miRNAs that were initially below the detection threshold but increased to detectable levels following sonobiopsy, miR-29c-5p, miR-125b-1-3p, miR-129-5p, miR-132-3p, miR-143-5p, miR-149-5p, miR-195-5p, miR-218-5p, miR-329-3p, and miR-1271-5p were associated with cancer- and glioma-related biological pathways.

These findings extend our prior work and support sonobiopsy as a spatially targeted, noninvasive multimodal liquid biopsy platform. By increasing the detectability of otherwise difficult-to-detect tumor-derived signals, sonobiopsy has the potential to advance the development of sensitive molecular diagnostics for glioma without surgery.