Cell-Free DNA Variant Sequencing Using Plasma and AR-V7 Testing of Circulating Tumor Cells in Prostate Cancer Patients

Prostate cancer (PCa) is the second most common malignant cancer and is a major cause of morbidity and mortality among men worldwide. There is still an urgent need for biomarkers applicable for diagnosis, prognosis, therapy prediction, or therapy monitoring in PCa. Liquid biopsies, including cell-fr...

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Autores principales:	Verena Lieb, Amer Abdulrahman, Katrin Weigelt, Siegfried Hauch, Michael Gombert, Juan Guzman, Laura Bellut, Peter J. Goebell, Robert Stöhr, Arndt Hartmann, Bernd Wullich, Helge Taubert, Sven Wach
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	prostate cancer cfDNA CTCs prognosis sequence variants Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0a3f909d9f53434e8e23bd99bd2a73cd
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spelling	oai:doaj.org-article:0a3f909d9f53434e8e23bd99bd2a73cd2021-11-25T17:13:02ZCell-Free DNA Variant Sequencing Using Plasma and AR-V7 Testing of Circulating Tumor Cells in Prostate Cancer Patients10.3390/cells101132232073-4409https://doaj.org/article/0a3f909d9f53434e8e23bd99bd2a73cd2021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3223https://doaj.org/toc/2073-4409Prostate cancer (PCa) is the second most common malignant cancer and is a major cause of morbidity and mortality among men worldwide. There is still an urgent need for biomarkers applicable for diagnosis, prognosis, therapy prediction, or therapy monitoring in PCa. Liquid biopsies, including cell-free DNA (cfDNA) and circulating tumor cells (CTCs), are a valuable source for studying such biomarkers and are minimally invasive. In our study, we investigated the cfDNA of 34 progressive PCa patients, via targeted sequencing, for sequence variants and for the occurrence of CTCs, with a focus on androgen receptor splice variant 7 (AR-V7)-positive CTCs. The cfDNA content was associated with overall survival (OS; <i>p</i> = 0.014), disease-specific survival (DSS; <i>p</i> = 0.004), and time to treatment change (TTC; <i>p</i> = 0.001). Moreover, when considering all sequence variants grouped by their functional impact and allele frequency, a significant association with TTC (<i>p</i> = 0.017) was observed. When investigating only pathogenic or likely pathogenic gene variants, variants of the BRCA1 gene (<i>p</i> = 0.029) and the AR ligand-binding domain (<i>p</i> = 0.050) were associated with a shorter TTC. Likewise, the presence of CTCs was associated with a shorter TTC (<i>p</i> = 0.031). The presence of AR-V7-positive CTCs was associated with TTC (<i>p</i> < 0.001) in Kaplan–Meier analysis. Interestingly, all patients with AR-V7-positive CTCs also carried TP53 point mutations. Altogether, analysis of cfDNA and CTCs can provide complementary information that may support temporal and targeted treatment decisions and may elucidate the optimal choice within the variety of therapy options for advanced PCa patients.Verena LiebAmer AbdulrahmanKatrin WeigeltSiegfried HauchMichael GombertJuan GuzmanLaura BellutPeter J. GoebellRobert StöhrArndt HartmannBernd WullichHelge TaubertSven WachMDPI AGarticleprostate cancercfDNACTCsprognosissequence variantsBiology (General)QH301-705.5ENCells, Vol 10, Iss 3223, p 3223 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	prostate cancer cfDNA CTCs prognosis sequence variants Biology (General) QH301-705.5
spellingShingle	prostate cancer cfDNA CTCs prognosis sequence variants Biology (General) QH301-705.5 Verena Lieb Amer Abdulrahman Katrin Weigelt Siegfried Hauch Michael Gombert Juan Guzman Laura Bellut Peter J. Goebell Robert Stöhr Arndt Hartmann Bernd Wullich Helge Taubert Sven Wach Cell-Free DNA Variant Sequencing Using Plasma and AR-V7 Testing of Circulating Tumor Cells in Prostate Cancer Patients
description	Prostate cancer (PCa) is the second most common malignant cancer and is a major cause of morbidity and mortality among men worldwide. There is still an urgent need for biomarkers applicable for diagnosis, prognosis, therapy prediction, or therapy monitoring in PCa. Liquid biopsies, including cell-free DNA (cfDNA) and circulating tumor cells (CTCs), are a valuable source for studying such biomarkers and are minimally invasive. In our study, we investigated the cfDNA of 34 progressive PCa patients, via targeted sequencing, for sequence variants and for the occurrence of CTCs, with a focus on androgen receptor splice variant 7 (AR-V7)-positive CTCs. The cfDNA content was associated with overall survival (OS; <i>p</i> = 0.014), disease-specific survival (DSS; <i>p</i> = 0.004), and time to treatment change (TTC; <i>p</i> = 0.001). Moreover, when considering all sequence variants grouped by their functional impact and allele frequency, a significant association with TTC (<i>p</i> = 0.017) was observed. When investigating only pathogenic or likely pathogenic gene variants, variants of the BRCA1 gene (<i>p</i> = 0.029) and the AR ligand-binding domain (<i>p</i> = 0.050) were associated with a shorter TTC. Likewise, the presence of CTCs was associated with a shorter TTC (<i>p</i> = 0.031). The presence of AR-V7-positive CTCs was associated with TTC (<i>p</i> < 0.001) in Kaplan–Meier analysis. Interestingly, all patients with AR-V7-positive CTCs also carried TP53 point mutations. Altogether, analysis of cfDNA and CTCs can provide complementary information that may support temporal and targeted treatment decisions and may elucidate the optimal choice within the variety of therapy options for advanced PCa patients.
format	article
author	Verena Lieb Amer Abdulrahman Katrin Weigelt Siegfried Hauch Michael Gombert Juan Guzman Laura Bellut Peter J. Goebell Robert Stöhr Arndt Hartmann Bernd Wullich Helge Taubert Sven Wach
author_facet	Verena Lieb Amer Abdulrahman Katrin Weigelt Siegfried Hauch Michael Gombert Juan Guzman Laura Bellut Peter J. Goebell Robert Stöhr Arndt Hartmann Bernd Wullich Helge Taubert Sven Wach
author_sort	Verena Lieb
title	Cell-Free DNA Variant Sequencing Using Plasma and AR-V7 Testing of Circulating Tumor Cells in Prostate Cancer Patients
title_short	Cell-Free DNA Variant Sequencing Using Plasma and AR-V7 Testing of Circulating Tumor Cells in Prostate Cancer Patients
title_full	Cell-Free DNA Variant Sequencing Using Plasma and AR-V7 Testing of Circulating Tumor Cells in Prostate Cancer Patients
title_fullStr	Cell-Free DNA Variant Sequencing Using Plasma and AR-V7 Testing of Circulating Tumor Cells in Prostate Cancer Patients
title_full_unstemmed	Cell-Free DNA Variant Sequencing Using Plasma and AR-V7 Testing of Circulating Tumor Cells in Prostate Cancer Patients
title_sort	cell-free dna variant sequencing using plasma and ar-v7 testing of circulating tumor cells in prostate cancer patients
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0a3f909d9f53434e8e23bd99bd2a73cd
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Cell-Free DNA Variant Sequencing Using Plasma and AR-V7 Testing of Circulating Tumor Cells in Prostate Cancer Patients

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