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
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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-11-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/11/3361 |
| _version_ | 1797548015905406976 |
|---|---|
| author | Matias A. Bustos Rebecca Gross Negin Rahimzadeh Hunter Cole Linh T. Tran Kevin D. Tran Ling Takeshima Stacey L. Stern Steven O’Day Dave S. B. Hoon |
| author_facet | Matias A. Bustos Rebecca Gross Negin Rahimzadeh Hunter Cole Linh T. Tran Kevin D. Tran Ling Takeshima Stacey L. Stern Steven O’Day Dave S. B. Hoon |
| author_sort | Matias A. Bustos |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T14:52:24Z |
| format | Article |
| id | doaj.art-ea0c7df471a34772b232ea2824430fbf |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T14:52:24Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ea0c7df471a34772b232ea2824430fbf2023-11-20T20:52:43ZengMDPI AGCancers2072-66942020-11-011211336110.3390/cancers12113361A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma PatientsMatias A. Bustos0Rebecca Gross1Negin Rahimzadeh2Hunter Cole3Linh T. Tran4Kevin D. Tran5Ling Takeshima6Stacey L. Stern7Steven O’Day8Dave S. B. Hoon9Department of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI), Providence Saint John’s Health Center (SJHC), Santa Monica, CA 90404, USADepartment of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI), Providence Saint John’s Health Center (SJHC), Santa Monica, CA 90404, USADepartment of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI), Providence Saint John’s Health Center (SJHC), Santa Monica, CA 90404, USADepartment of Immuno-Oncology and Clinical Research, JWCI, Providence SJHC, Santa Monica, CA 90404, USADepartment of Genomic Sequencing Center, JWCI, Providence SJHC, Santa Monica, CA 90404, USADepartment of Genomic Sequencing Center, JWCI, Providence SJHC, Santa Monica, CA 90404, USADepartment of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI), Providence Saint John’s Health Center (SJHC), Santa Monica, CA 90404, USADepartment of Biostatistics, JWCI, Providence SJHC, Santa Monica, CA 90404, USADepartment of Immuno-Oncology and Clinical Research, JWCI, Providence SJHC, Santa Monica, CA 90404, USADepartment of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI), Providence Saint John’s Health Center (SJHC), Santa Monica, CA 90404, USASerum 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.https://www.mdpi.com/2072-6694/12/11/3361serum LDHblood biomarkermiRNAcirculating microRNAplasmaimmunotherapy |
| spellingShingle | Matias A. Bustos Rebecca Gross Negin Rahimzadeh Hunter Cole Linh T. Tran Kevin D. Tran Ling Takeshima Stacey L. Stern Steven O’Day Dave S. B. Hoon 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 serum LDH blood biomarker miRNA circulating microRNA plasma immunotherapy |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | serum LDH blood biomarker miRNA circulating microRNA plasma immunotherapy |
| url | https://www.mdpi.com/2072-6694/12/11/3361 |
| work_keys_str_mv | AT matiasabustos apilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT rebeccagross apilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT neginrahimzadeh apilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT huntercole apilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT linhttran apilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT kevindtran apilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT lingtakeshima apilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT staceylstern apilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT stevenoday apilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT davesbhoon apilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT matiasabustos pilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT rebeccagross pilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT neginrahimzadeh pilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT huntercole pilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT linhttran pilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT kevindtran pilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT lingtakeshima pilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT staceylstern pilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT stevenoday pilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients AT davesbhoon pilotstudycomparingtheefficacyoflactatedehydrogenaselevelsversuscirculatingcellfreemicrornasinmonitoringresponsestocheckpointinhibitorimmunotherapyinmetastaticmelanomapatients |