miRNAs in Serum Exosomes for Differential Diagnosis of Brain Metastases

SIMPLE SUMMARY: Current methods for the detection of brain malignancies often display low sensitivity and specificity. Noninvasive biomarkers can complement imaging techniques to improve the diagnosis of these tumors. The aim of this study was to identify circulating miRNAs in serum exosomes useful in all phases of the diagnostic and therapeutic path of patients with malignant brain lesions. Our data show a signature of exosomal miRNAs useful for the differential diagnosis of brain metastases and for monitoring tumor evolution over time. ABSTRACT: Circulating miRNAs are increasingly studied and proposed as tumor markers with the aim of investigating their role in monitoring the response to therapy as well as the natural evolution of primary or secondary brain tumors. This study aimed to evaluate the modulation of the expression of three miRNAs, miR-21, miR-222 and miR-124-3p, in the serum exosomes of patients with high-grade gliomas (HGGs) and brain metastases (BMs) to verify their usefulness in the differential diagnosis of brain masses; then, it focused on their variations following the surgical and/or radiosurgical treatment of the BMs. A total of 105 patients with BMs from primary lung or breast cancer, or melanoma underwent neurosurgery or radiosurgery treatment, and 91 patients with HGGs were enrolled, along with 30 healthy controls. A significant increase in miR-21 expression in serum exosomes was observed in both HGGs and BMs compared with healthy controls; on the other hand, miR-124-3p was significantly decreased in BMs, and it was increased in HGGs. After the surgical or radiosurgical treatment of patients with BMs, a significant reduction in miR-21 was noted with both types of treatments. This study identified a signature of exosomal miRNAs that could be useful as a noninvasive complementary analysis both in the differential diagnosis of BMs from glial tumors and in providing information on tumor evolution over time.