Integrated Assessment of Circulating Cell-Free MicroRNA Signatures in Plasma of Patients with Melanoma Brain Metastasis

We analyzed cell-free microRNAs (cfmiRs) in blood, tissue, and urine samples of melanoma patients to find potential biomarkers for monitoring and assessing early detection of melanoma metastasis. This study demonstrates that identifying cfmiR signatures in body fluids may allow for detection and assessment of melanoma brain metastasis (MBM) and metastatic melanoma patients undergoing checkpoint inhibitor immunotherapy treatments. Overall design: Data was extracted from patients' blood, urine, and tissue. Samples were profiled for cfmiRs by using a next generation sequencing (NGS) probe-based HTG EdgeSeq miRNA whole transcriptome assay. 2083 microRNAs were profiled for 409 clinical specimens. Normal (cancer-free) donor plasma (n=48) and serum plasma (n=48) samples were analyzed in duplicates. Pre-surgery plasma from melanoma brain metastasis patients (MBM, n=36) were compared for differences in their cfmiR counts, and then verified in a second cohort of MBM plasma samples (n = 24). A cfmiR signature was identified in MBM plasma samples, and further verified in MBM tumor tissues (n=24). MBM cfmiR signature was specifically compared to patients with other cancer types that had brain metastasis (LuBM, n=6 and BCBM, n=7) and glioblastomas (n=36). In addition, the detection of cfmiRs in pre- and post-treatment plasma (n=20) and urine (n=14) samples collected from metastatic melanoma patients receiving checkpoint inhibitor immunotherapy (CII) showed potential utility in assessing CII responses. Normal urine samples (n=8) in duplicates were analyzed to demonstrate reproducibility and compared to urine from metastatic melanoma patients.