Integrated Assessment of Circulating Cell-Free MicroRNA Signatures in Plasma of Patients with Melanoma Brain Metastasis
by
Matias A. Bustos 1
, Kevin D. Tran 2, Negin Rahimzadeh 1, Rebecca Gross 1, Selena Y. Lin 1, Yoshiaki Shoji 1, Tomohiro Murakami 1, Christine L. Boley 3, Linh T. Tran 2, Hunter Cole 3, Daniel F. Kelly 4, Steven O’Day 3 and Dave S. B. Hoon 1,2,*
Matias A. Bustos 1, Kevin D. Tran 2, Negin Rahimzadeh 1, Rebecca Gross 1, Selena Y. Lin 1, Yoshiaki Shoji 1, Tomohiro Murakami 1, Christine L. Boley 3, Linh T. Tran 2, Hunter Cole 3, Daniel F. Kelly 4, Steven O’Day 3 and Dave S. B. Hoon 1,2,*
1
Department of Translational Molecular Medicine, John Wayne Cancer Institute at Providence Saint John’s Health Center, Santa Monica, CA 90404, USA
2
Department of Genomic Sequencing Center, John Wayne Cancer Institute at Providence Saint John’s Health Center, Santa Monica, CA 90404, USA
3
Department of Immuno-Oncology and Clinical Research, John Wayne Cancer Institute, Santa Monica, CA 90404, USA
4
Pacific Neuroscience Institute, John Wayne Cancer Institute, Saint John’s Health Center, Santa Monica, CA 90404, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(6), 1692; https://doi.org/10.3390/cancers12061692
Received: 4 May 2020 / Revised: 23 June 2020 / Accepted: 23 June 2020 / Published: 25 June 2020
(This article belongs to the Special Issue Liquid Biopsy: Latest Advances and Future Challenges)
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.
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Keywords:
cell-free miRNA; melanoma; brain metastasis; plasma; urine; blood; NGS; glioblastoma; immunotherapy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Bustos, M.A.; Tran, K.D.; Rahimzadeh, N.; Gross, R.; Lin, S.Y.; Shoji, Y.; Murakami, T.; Boley, C.L.; Tran, L.T.; Cole, H.; Kelly, D.F.; O’Day, S.; Hoon, D.S.B. Integrated Assessment of Circulating Cell-Free MicroRNA Signatures in Plasma of Patients with Melanoma Brain Metastasis. Cancers 2020, 12, 1692.
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