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Epigenetic Analysis of Circulating Tumor DNA in Localized and Metastatic Prostate Cancer: Evaluation of Clinical Biomarker Potential
Novel and minimally-invasive prostate cancer (PCa)-specific biomarkers are needed to improve diagnosis and risk stratification. Here, we investigated the biomarker potential in localized and de novo metastatic PCa (mPCa) of methylated circulating tumor DNA (ctDNA) in plasma. Using the Marmal-aid dat...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349912/ https://www.ncbi.nlm.nih.gov/pubmed/32486483 http://dx.doi.org/10.3390/cells9061362 |
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author | Bjerre, Marianne Trier Nørgaard, Maibritt Larsen, Ole Halfdan Jensen, Sarah Østrup Strand, Siri H. Østergren, Peter Fode, Mikkel Fredsøe, Jacob Ulhøi, Benedicte Parm Mortensen, Martin Mørck Jensen, Jørgen Bjerggaard Borre, Michael Sørensen, Karina D. |
author_facet | Bjerre, Marianne Trier Nørgaard, Maibritt Larsen, Ole Halfdan Jensen, Sarah Østrup Strand, Siri H. Østergren, Peter Fode, Mikkel Fredsøe, Jacob Ulhøi, Benedicte Parm Mortensen, Martin Mørck Jensen, Jørgen Bjerggaard Borre, Michael Sørensen, Karina D. |
author_sort | Bjerre, Marianne Trier |
collection | PubMed |
description | Novel and minimally-invasive prostate cancer (PCa)-specific biomarkers are needed to improve diagnosis and risk stratification. Here, we investigated the biomarker potential in localized and de novo metastatic PCa (mPCa) of methylated circulating tumor DNA (ctDNA) in plasma. Using the Marmal-aid database and in-house datasets, we identified three top candidates specifically hypermethylated in PCa tissue: DOCK2, HAPLN3, and FBXO30 (specificity/sensitivity: 80%–100%/75–94%). These candidates were further analyzed in plasma samples from 36 healthy controls, 61 benign prostatic hyperplasia (BPH), 102 localized PCa, and 65 de novo mPCa patients using methylation-specific droplet digital PCR. Methylated ctDNA for DOCK2/HAPLN3/FBXO30 was generally not detected in healthy controls, BPH patients, nor in patients with localized PCa despite a positive signal in 98%–100% of matched radical prostatectomy tissue samples. However, ctDNA methylation of DOCK2, HAPLN3, and/or FBXO30 was detected in 61.5% (40/65) of de novo mPCa patients and markedly increased in high- compared to low-volume mPCa (89.3% (25/28) vs. 32.1% (10/31), p < 0.001). Moreover, detection of methylated ctDNA was associated with significantly shorter time to progression to metastatic castration resistant PCa, independent of tumor-volume. These results indicate that methylated ctDNA (DOCK2/HAPLN3/FBXO30) may be potentially useful for identification of hormone-naïve mPCa patients who could benefit from intensified treatment. |
format | Online Article Text |
id | pubmed-7349912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73499122020-07-15 Epigenetic Analysis of Circulating Tumor DNA in Localized and Metastatic Prostate Cancer: Evaluation of Clinical Biomarker Potential Bjerre, Marianne Trier Nørgaard, Maibritt Larsen, Ole Halfdan Jensen, Sarah Østrup Strand, Siri H. Østergren, Peter Fode, Mikkel Fredsøe, Jacob Ulhøi, Benedicte Parm Mortensen, Martin Mørck Jensen, Jørgen Bjerggaard Borre, Michael Sørensen, Karina D. Cells Article Novel and minimally-invasive prostate cancer (PCa)-specific biomarkers are needed to improve diagnosis and risk stratification. Here, we investigated the biomarker potential in localized and de novo metastatic PCa (mPCa) of methylated circulating tumor DNA (ctDNA) in plasma. Using the Marmal-aid database and in-house datasets, we identified three top candidates specifically hypermethylated in PCa tissue: DOCK2, HAPLN3, and FBXO30 (specificity/sensitivity: 80%–100%/75–94%). These candidates were further analyzed in plasma samples from 36 healthy controls, 61 benign prostatic hyperplasia (BPH), 102 localized PCa, and 65 de novo mPCa patients using methylation-specific droplet digital PCR. Methylated ctDNA for DOCK2/HAPLN3/FBXO30 was generally not detected in healthy controls, BPH patients, nor in patients with localized PCa despite a positive signal in 98%–100% of matched radical prostatectomy tissue samples. However, ctDNA methylation of DOCK2, HAPLN3, and/or FBXO30 was detected in 61.5% (40/65) of de novo mPCa patients and markedly increased in high- compared to low-volume mPCa (89.3% (25/28) vs. 32.1% (10/31), p < 0.001). Moreover, detection of methylated ctDNA was associated with significantly shorter time to progression to metastatic castration resistant PCa, independent of tumor-volume. These results indicate that methylated ctDNA (DOCK2/HAPLN3/FBXO30) may be potentially useful for identification of hormone-naïve mPCa patients who could benefit from intensified treatment. MDPI 2020-05-31 /pmc/articles/PMC7349912/ /pubmed/32486483 http://dx.doi.org/10.3390/cells9061362 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bjerre, Marianne Trier Nørgaard, Maibritt Larsen, Ole Halfdan Jensen, Sarah Østrup Strand, Siri H. Østergren, Peter Fode, Mikkel Fredsøe, Jacob Ulhøi, Benedicte Parm Mortensen, Martin Mørck Jensen, Jørgen Bjerggaard Borre, Michael Sørensen, Karina D. Epigenetic Analysis of Circulating Tumor DNA in Localized and Metastatic Prostate Cancer: Evaluation of Clinical Biomarker Potential |
title | Epigenetic Analysis of Circulating Tumor DNA in Localized and Metastatic Prostate Cancer: Evaluation of Clinical Biomarker Potential |
title_full | Epigenetic Analysis of Circulating Tumor DNA in Localized and Metastatic Prostate Cancer: Evaluation of Clinical Biomarker Potential |
title_fullStr | Epigenetic Analysis of Circulating Tumor DNA in Localized and Metastatic Prostate Cancer: Evaluation of Clinical Biomarker Potential |
title_full_unstemmed | Epigenetic Analysis of Circulating Tumor DNA in Localized and Metastatic Prostate Cancer: Evaluation of Clinical Biomarker Potential |
title_short | Epigenetic Analysis of Circulating Tumor DNA in Localized and Metastatic Prostate Cancer: Evaluation of Clinical Biomarker Potential |
title_sort | epigenetic analysis of circulating tumor dna in localized and metastatic prostate cancer: evaluation of clinical biomarker potential |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349912/ https://www.ncbi.nlm.nih.gov/pubmed/32486483 http://dx.doi.org/10.3390/cells9061362 |
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