Sonobiopsy for enrichment of circulating microRNAs in glioma patients

Background 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 miRNAs. Methods Eleven patients with glioma underwent FUS sonication immediately prior to surgical resection. Peripheral blood samples were collected 5 minutes before and 5, 10, and 30 minutes after sonication. Plasma and brain tissue miRNA levels were quantified through small RNA sequencing and compared among different time points. Results Plasma miRNAs of tumor-derived 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 minutes. In contrast, miRNAs above the detection threshold (RPM ≥10) exhibited no significant change following FUS. 12 miRNAs were enriched after sonobiopsy and particularly 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. Conclusions These findings extend our prior ctDNA sonobiopsy 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.