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

Publication Title

Cancers (Basel)

Authors

Matias Bustos, Division of Molecular Oncology, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.Follow
Kevin Tran, Division of Molecular Oncology, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, California.Follow
Negin Rahimzadeh, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA.Follow
Rebecca Gross, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA.Follow
Selena Y Lin, Department of Translational Molecular Medicine, John Wayne Cancer Institute, Santa Monica, CA, USAFollow
Yoshiaki Shoji, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA.Follow
Tomohiro Murakami, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA.
Christine L Boley, Department of Immuno-Oncology and Clinical Research, John Wayne Cancer Institute, PHS, Santa Monica, CA.Follow
Linh T Tran, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA.Follow
Hunter Cole, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA.Follow
Daniel F Kelly, Pacific Neuroscience Institute, Brain Tumor Center & Pituitary Disorders Program, John Wayne Cancer Institute at Providence Saint John's Health Center, 2200 Santa Monica Blvd., Santa Monica, CA, 90404, USA.Follow
Steven J O'Day, The John Wayne Cancer Institute, Providence Saint John's Health Center, Santa Monica, CAFollow
Dave Hoon, Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA.Follow

Document Type

Article

Publication Date

6-25-2020

Abstract

Primary cutaneous melanoma frequently metastasizes to distant organs including the brain. Identification of cell-free microRNAs (cfmiRs) found in the blood can be used as potential body fluid biomarkers for detecting and monitoring patients with melanoma brain metastasis (MBM). In this pilot study, we initially aimed to identify cfmiRs in the blood of MBM patients. Normal donors plasma (healthy, n = 48) and pre-operative MBM patients' plasma samples (n = 36) were compared for differences in >2000 microRNAs (miRs) using a next generation sequencing (NGS) probe-based assay. A 74 cfmiR signature was identified in an initial cohort of MBM plasma samples and then verified in a second cohort of MBM plasma samples (n = 24). Of these, only 58 cfmiRs were also detected in MBM tissues (n = 24). CfmiR signatures were also found in patients who have lung and breast cancer brain metastasis (n = 13) and glioblastomas (n = 36) compared to MBM plasma samples. The 74 cfmiR signature and the latter cfmiR signatures were then compared. We found a 6 cfmiR signature that was commonly upregulated in MBM plasma samples in all of the comparisons, and a 29 cfmiR signature that distinguishes MBM patients from normal donors' samples. In addition, we assessed for cfmiRs in plasma (n = 20) and urine (n = 14) samples collected from metastatic melanoma patients receiving checkpoint inhibitor immunotherapy (CII). Pre- and post-treatment samples showed consistent changes in cfmiRs. Analysis of pre- and post-treatment plasma samples showed 8 differentially expressed (DE) cfmiRs that overlapped with the 35 cfmiR signature found in MBM patients. In paired pre-treatment plasma and urine samples receiving CII 8 cfmiRs overlapped. This study identified specific cfmiRs in MBM plasma samples that may potentially allow for assessment of melanoma patients developing MBM. The cfmiR signatures identified in both blood and urine may have potential utility to assess CII responses after further validation.

Clinical Institute

Cancer

Clinical Institute

Neurosciences (Brain & Spine)

Specialty/Research Institute

Oncology

Specialty/Research Institute

Neurosciences