Blood-Based DNA Methylation Analysis by Multiplexed OBBPA-ddPCR to Verify Indications for Prostate Biopsies in Suspected Prostate Cancer Patients
Current prostate carcinoma (PCa) biomarkers, including total prostate-specific antigen (tPSA), have unsatisfactory diagnostic sensitivity and specificity resulting in overdiagnosis and overtreatment. Previously, we described an optimised bias-based preamplification-digital droplet PCR (OBBPA-ddPCR)...
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| Veröffentlicht in: | Cancers 2024-04, Vol.16 (7), p.1324 |
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| creator | Friedemann, Markus Jandeck, Carsten Tautz, Lars Gutewort, Katharina von Rein, Lisa Sukocheva, Olga Fuessel, Susanne Menschikowski, Mario |
| description | Current prostate carcinoma (PCa) biomarkers, including total prostate-specific antigen (tPSA), have unsatisfactory diagnostic sensitivity and specificity resulting in overdiagnosis and overtreatment. Previously, we described an optimised bias-based preamplification-digital droplet PCR (OBBPA-ddPCR) technique, which detects tumour DNA in blood-derived cell-free DNA (cfDNA) of cancer patients. The current study investigated the performance of newly developed OBBPA-ddPCR-based biomarkers. Blood plasma samples from healthy individuals (
= 90, controls) and PCa (
= 39) and benign prostatic hyperplasia patients (BPH,
= 40) were analysed. PCa and BPH patients had tPSA values within a diagnostic grey area of 2-15 ng/mL, for whom further diagnostic validation is most crucial. Methylation levels of biomarkers
,
,
, and
were found significantly increased in PCa patients compared to controls. By combining classical PCa risk factors (percentage of free PSA compared to tPSA (QfPSA) and patient's age) with cfDNA-based biomarkers, we developed PCa risk scores with improved sensitivity and specificity compared to established tPSA and QfPSA single-marker analyses. The diagnostic specificity was increased to 70% with 100% sensitivity for clinically significant PCa patients. Thus, prostate biopsies could be avoided for 28 out of 40 BPH patients. In conclusion, the newly developed risk scores may help to confirm the clinical decision and prevent unnecessary prostate biopsy. |
| doi_str_mv | 10.3390/cancers16071324 |
| format | Article |
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= 90, controls) and PCa (
= 39) and benign prostatic hyperplasia patients (BPH,
= 40) were analysed. PCa and BPH patients had tPSA values within a diagnostic grey area of 2-15 ng/mL, for whom further diagnostic validation is most crucial. Methylation levels of biomarkers
,
,
, and
were found significantly increased in PCa patients compared to controls. By combining classical PCa risk factors (percentage of free PSA compared to tPSA (QfPSA) and patient's age) with cfDNA-based biomarkers, we developed PCa risk scores with improved sensitivity and specificity compared to established tPSA and QfPSA single-marker analyses. The diagnostic specificity was increased to 70% with 100% sensitivity for clinically significant PCa patients. Thus, prostate biopsies could be avoided for 28 out of 40 BPH patients. In conclusion, the newly developed risk scores may help to confirm the clinical decision and prevent unnecessary prostate biopsy.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers16071324</identifier><identifier>PMID: 38611002</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Biomarkers ; Biopsy ; Blood ; Cancer ; Cancer patients ; Care and treatment ; Clinical significance ; Disease ; DNA ; DNA methylation ; Epigenetics ; Ethylenediaminetetraacetic acid ; Genetic testing ; Hyperplasia ; Methylation ; Mortality ; Nucleotide sequence ; Oncology, Experimental ; Patients ; Plasma ; Polymerase chain reaction ; Prevention ; Prostate cancer ; Prostate carcinoma ; Prostate-specific antigen ; Risk factors</subject><ispartof>Cancers, 2024-04, Vol.16 (7), p.1324</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 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 (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c387t-d705edefcee490214672e5cedbce529e52c9d7579867d5d2ac8a6a1b89d146973</cites><orcidid>0000-0002-5339-9460 ; 0000-0003-1041-3311 ; 0000-0001-5820-8988</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38611002$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Friedemann, Markus</creatorcontrib><creatorcontrib>Jandeck, Carsten</creatorcontrib><creatorcontrib>Tautz, Lars</creatorcontrib><creatorcontrib>Gutewort, Katharina</creatorcontrib><creatorcontrib>von Rein, Lisa</creatorcontrib><creatorcontrib>Sukocheva, Olga</creatorcontrib><creatorcontrib>Fuessel, Susanne</creatorcontrib><creatorcontrib>Menschikowski, Mario</creatorcontrib><title>Blood-Based DNA Methylation Analysis by Multiplexed OBBPA-ddPCR to Verify Indications for Prostate Biopsies in Suspected Prostate Cancer Patients</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Current prostate carcinoma (PCa) biomarkers, including total prostate-specific antigen (tPSA), have unsatisfactory diagnostic sensitivity and specificity resulting in overdiagnosis and overtreatment. Previously, we described an optimised bias-based preamplification-digital droplet PCR (OBBPA-ddPCR) technique, which detects tumour DNA in blood-derived cell-free DNA (cfDNA) of cancer patients. The current study investigated the performance of newly developed OBBPA-ddPCR-based biomarkers. Blood plasma samples from healthy individuals (
= 90, controls) and PCa (
= 39) and benign prostatic hyperplasia patients (BPH,
= 40) were analysed. PCa and BPH patients had tPSA values within a diagnostic grey area of 2-15 ng/mL, for whom further diagnostic validation is most crucial. Methylation levels of biomarkers
,
,
, and
were found significantly increased in PCa patients compared to controls. By combining classical PCa risk factors (percentage of free PSA compared to tPSA (QfPSA) and patient's age) with cfDNA-based biomarkers, we developed PCa risk scores with improved sensitivity and specificity compared to established tPSA and QfPSA single-marker analyses. The diagnostic specificity was increased to 70% with 100% sensitivity for clinically significant PCa patients. Thus, prostate biopsies could be avoided for 28 out of 40 BPH patients. In conclusion, the newly developed risk scores may help to confirm the clinical decision and prevent unnecessary prostate biopsy.</description><subject>Biomarkers</subject><subject>Biopsy</subject><subject>Blood</subject><subject>Cancer</subject><subject>Cancer patients</subject><subject>Care and treatment</subject><subject>Clinical significance</subject><subject>Disease</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Epigenetics</subject><subject>Ethylenediaminetetraacetic acid</subject><subject>Genetic testing</subject><subject>Hyperplasia</subject><subject>Methylation</subject><subject>Mortality</subject><subject>Nucleotide sequence</subject><subject>Oncology, Experimental</subject><subject>Patients</subject><subject>Plasma</subject><subject>Polymerase chain reaction</subject><subject>Prevention</subject><subject>Prostate cancer</subject><subject>Prostate carcinoma</subject><subject>Prostate-specific antigen</subject><subject>Risk factors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptkstu3SAQhq2qUROlWXdXIXXTjRMwNpilfXqLlMtRb1uLA-OWiAMOYKl-jL5xyUmaNlEYIUbw_b9gmKJ4RfAxpQKfKOkUhEgY5oRW9bPioMK8KhkT9fP_8v3iKMYrnAelhDP-otinLSME4-qg-N1b73XZywgavbvo0Dmkn4uVyXiHOiftEk1EmwWdzzaZycKvzF32_bortV6vPqPk0XcIZlzQqdNG7YQRjT6gdfAxyQSoN36KBiIyDn2Z4wQqZZP749XuGWidpeBSfFnsjdJGOLpbD4tvH95_XX0qzy4_nq66s1LRlqdSc9yAhlEB1AJXpGa8gkaB3ihoKpGnEpo3XLSM60ZXUrWSSbJphc6s4PSweHvrOwV_PUNMw9ZEBdZKB36OA8W0rWtMGc7om0folZ9DLs6O4pmjpP1H_ZAWBuNGn4JUN6ZDxwXGhDdYZOr4CSqHhq1R3sFo8v4DwcmtQOWCxQDjMAWzlWEZCB5u-mB41AdZ8fruuvNmC_qe__vr9A88wa4V</recordid><startdate>20240401</startdate><enddate>20240401</enddate><creator>Friedemann, Markus</creator><creator>Jandeck, Carsten</creator><creator>Tautz, Lars</creator><creator>Gutewort, Katharina</creator><creator>von Rein, Lisa</creator><creator>Sukocheva, Olga</creator><creator>Fuessel, Susanne</creator><creator>Menschikowski, Mario</creator><general>MDPI AG</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5339-9460</orcidid><orcidid>https://orcid.org/0000-0003-1041-3311</orcidid><orcidid>https://orcid.org/0000-0001-5820-8988</orcidid></search><sort><creationdate>20240401</creationdate><title>Blood-Based DNA Methylation Analysis by Multiplexed OBBPA-ddPCR to Verify Indications for Prostate Biopsies in Suspected Prostate Cancer Patients</title><author>Friedemann, Markus ; Jandeck, Carsten ; Tautz, Lars ; Gutewort, Katharina ; von Rein, Lisa ; Sukocheva, Olga ; Fuessel, Susanne ; Menschikowski, Mario</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-d705edefcee490214672e5cedbce529e52c9d7579867d5d2ac8a6a1b89d146973</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Biomarkers</topic><topic>Biopsy</topic><topic>Blood</topic><topic>Cancer</topic><topic>Cancer patients</topic><topic>Care and treatment</topic><topic>Clinical significance</topic><topic>Disease</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>Epigenetics</topic><topic>Ethylenediaminetetraacetic acid</topic><topic>Genetic testing</topic><topic>Hyperplasia</topic><topic>Methylation</topic><topic>Mortality</topic><topic>Nucleotide sequence</topic><topic>Oncology, Experimental</topic><topic>Patients</topic><topic>Plasma</topic><topic>Polymerase chain reaction</topic><topic>Prevention</topic><topic>Prostate cancer</topic><topic>Prostate carcinoma</topic><topic>Prostate-specific antigen</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Friedemann, Markus</creatorcontrib><creatorcontrib>Jandeck, Carsten</creatorcontrib><creatorcontrib>Tautz, Lars</creatorcontrib><creatorcontrib>Gutewort, Katharina</creatorcontrib><creatorcontrib>von Rein, Lisa</creatorcontrib><creatorcontrib>Sukocheva, Olga</creatorcontrib><creatorcontrib>Fuessel, Susanne</creatorcontrib><creatorcontrib>Menschikowski, Mario</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Friedemann, Markus</au><au>Jandeck, Carsten</au><au>Tautz, Lars</au><au>Gutewort, Katharina</au><au>von Rein, Lisa</au><au>Sukocheva, Olga</au><au>Fuessel, Susanne</au><au>Menschikowski, Mario</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Blood-Based DNA Methylation Analysis by Multiplexed OBBPA-ddPCR to Verify Indications for Prostate Biopsies in Suspected Prostate Cancer Patients</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2024-04-01</date><risdate>2024</risdate><volume>16</volume><issue>7</issue><spage>1324</spage><pages>1324-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Current prostate carcinoma (PCa) biomarkers, including total prostate-specific antigen (tPSA), have unsatisfactory diagnostic sensitivity and specificity resulting in overdiagnosis and overtreatment. Previously, we described an optimised bias-based preamplification-digital droplet PCR (OBBPA-ddPCR) technique, which detects tumour DNA in blood-derived cell-free DNA (cfDNA) of cancer patients. The current study investigated the performance of newly developed OBBPA-ddPCR-based biomarkers. Blood plasma samples from healthy individuals (
= 90, controls) and PCa (
= 39) and benign prostatic hyperplasia patients (BPH,
= 40) were analysed. PCa and BPH patients had tPSA values within a diagnostic grey area of 2-15 ng/mL, for whom further diagnostic validation is most crucial. Methylation levels of biomarkers
,
,
, and
were found significantly increased in PCa patients compared to controls. By combining classical PCa risk factors (percentage of free PSA compared to tPSA (QfPSA) and patient's age) with cfDNA-based biomarkers, we developed PCa risk scores with improved sensitivity and specificity compared to established tPSA and QfPSA single-marker analyses. The diagnostic specificity was increased to 70% with 100% sensitivity for clinically significant PCa patients. Thus, prostate biopsies could be avoided for 28 out of 40 BPH patients. In conclusion, the newly developed risk scores may help to confirm the clinical decision and prevent unnecessary prostate biopsy.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38611002</pmid><doi>10.3390/cancers16071324</doi><orcidid>https://orcid.org/0000-0002-5339-9460</orcidid><orcidid>https://orcid.org/0000-0003-1041-3311</orcidid><orcidid>https://orcid.org/0000-0001-5820-8988</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Biomarkers Biopsy Blood Cancer Cancer patients Care and treatment Clinical significance Disease DNA DNA methylation Epigenetics Ethylenediaminetetraacetic acid Genetic testing Hyperplasia Methylation Mortality Nucleotide sequence Oncology, Experimental Patients Plasma Polymerase chain reaction Prevention Prostate cancer Prostate carcinoma Prostate-specific antigen Risk factors |
| title | Blood-Based DNA Methylation Analysis by Multiplexed OBBPA-ddPCR to Verify Indications for Prostate Biopsies in Suspected Prostate Cancer Patients |
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