Next Article in Journal
ShcD Binds DOCK4, Promotes Ameboid Motility and Metastasis Dissemination, Predicting Poor Prognosis in Melanoma
Next Article in Special Issue
Circulating Exosomal MicroRNA-1307-5p as a Predictor for Metastasis in Patients with Hepatocellular Carcinoma
Previous Article in Journal
Radiation Induced Upregulation of DNA Sensing Pathways is Cell-Type Dependent and Can Mediate the Off-Target Effects
Previous Article in Special Issue
MiRNA-103/107 in Primary High-Grade Serous Ovarian Cancer and Its Clinical Significance
Article

A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients

1
Department of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI), Providence Saint John’s Health Center (SJHC), Santa Monica, CA 90404, USA
2
Department of Immuno-Oncology and Clinical Research, JWCI, Providence SJHC, Santa Monica, CA 90404, USA
3
Department of Genomic Sequencing Center, JWCI, Providence SJHC, Santa Monica, CA 90404, USA
4
Department of Biostatistics, JWCI, Providence SJHC, Santa Monica, CA 90404, USA
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(11), 3361; https://doi.org/10.3390/cancers12113361
Received: 9 September 2020 / Accepted: 9 November 2020 / Published: 13 November 2020
(This article belongs to the Special Issue MicroRNA and Cancer)
Improvement in melanoma patients with metastatic disease is needed to better assess immunotherapies. Lactate dehydrogenase (LDH) is currently an accepted biomarker for stage IV, but it has limited utility for stage III melanoma patients. Thus, finding biomarkers for metastatic melanoma is important not only to identify progressive melanoma tumors, but also to monitor patients under checkpoint inhibitor immunotherapy (CII). The aim of this pilot study was to demonstrate the utility of circulating cell-free microRNAs (cfmiRs) as potential blood biomarkers for stage III and IV melanoma patients compared to LDH. To accomplish this aim, we profiled for cfmiR the plasma of metastatic melanoma patients before and during CII treatment, and compared them to normal healthy donors’ samples. The cfmiR profiling was performed using an NGS-based miRNA assay, which requires no extraction and a small volume input. We found specific cfmiR signatures in stage III and IV metastatic melanoma patients. As a proof of concept, our results showed that certain cfmiRs are associated with CII outcomes.
Serum lactate dehydrogenase (LDH) is a standard prognostic biomarker for stage IV melanoma patients. Often, LDH levels do not provide real-time information about the metastatic melanoma patients’ disease status and treatment response. Therefore, there is a need to find reliable blood biomarkers for improved monitoring of metastatic melanoma patients who are undergoing checkpoint inhibitor immunotherapy (CII). The objective in this prospective pilot study was to discover circulating cell-free microRNA (cfmiR) signatures in the plasma that could assess melanoma patients’ responses during CII. The cfmiRs were evaluated by the next-generation sequencing (NGS) HTG EdgeSeq microRNA (miR) Whole Transcriptome Assay (WTA; 2083 miRs) in 158 plasma samples obtained before and during the course of CII from 47 AJCC stage III/IV melanoma patients’ and 73 normal donors’ plasma samples. Initially, cfmiR profiles for pre- and post-treatment plasma samples of stage IV non-responder melanoma patients were compared to normal donors’ plasma samples. Using machine learning, we identified a 9 cfmiR signature that was associated with stage IV melanoma patients being non-responsive to CII. These cfmiRs were compared in pre- and post-treatment plasma samples from stage IV melanoma patients that showed good responses. Circulating miR-4649-3p, miR-615-3p, and miR-1234-3p demonstrated potential prognostic utility in assessing CII responses. Compared to LDH levels during CII, circulating miR-615-3p levels were consistently more efficient in detecting melanoma patients undergoing CII who developed progressive disease. By combining stage III/IV patients, 92 and 17 differentially expressed cfmiRs were identified in pre-treatment plasma samples from responder and non-responder patients, respectively. In conclusion, this pilot study demonstrated cfmiRs that identified treatment responses and could allow for real-time monitoring of patients receiving CII. View Full-Text
Keywords: serum LDH; blood biomarker; miRNA; circulating microRNA; plasma; immunotherapy; immune checkpoint inhibitors; metastatic melanoma serum LDH; blood biomarker; miRNA; circulating microRNA; plasma; immunotherapy; immune checkpoint inhibitors; metastatic melanoma
Show Figures

Graphical abstract

MDPI and ACS Style

Bustos, M.A.; Gross, R.; Rahimzadeh, N.; Cole, H.; Tran, L.T.; Tran, K.D.; Takeshima, L.; Stern, S.L.; O’Day, S.; Hoon, D.S.B. A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients. Cancers 2020, 12, 3361. https://doi.org/10.3390/cancers12113361

AMA Style

Bustos MA, Gross R, Rahimzadeh N, Cole H, Tran LT, Tran KD, Takeshima L, Stern SL, O’Day S, Hoon DSB. A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients. Cancers. 2020; 12(11):3361. https://doi.org/10.3390/cancers12113361

Chicago/Turabian Style

Bustos, Matias A., Rebecca Gross, Negin Rahimzadeh, Hunter Cole, Linh T. Tran, Kevin D. Tran, Ling Takeshima, Stacey L. Stern, Steven O’Day, and Dave S.B. Hoon. 2020. "A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients" Cancers 12, no. 11: 3361. https://doi.org/10.3390/cancers12113361

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop