Bladder Cancer detection by urinary methylation markers GHSR/MAL: a validation study
Purpose Although cystoscopy is a reliable tool for detecting bladder cancer, it poses a high burden on patients and entails high costs. This highlights the need for non-invasive and cost-effective alternatives. This study aimed to validate a previously developed urinary methylation marker panel cont...
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| Veröffentlicht in: | World journal of urology 2024-10, Vol.42 (1), p.578, Article 578 |
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| creator | Beijert, I. J. van den Burgt, Y. Hentschel, A. E. Bosschieter, J. Kauer, P. C. Lissenberg-Witte, B. I. van Moorselaar, R. J.A. Nieuwenhuijzen, J. A. Steenbergen, R. D.M. |
| description | Purpose
Although cystoscopy is a reliable tool for detecting bladder cancer, it poses a high burden on patients and entails high costs. This highlights the need for non-invasive and cost-effective alternatives. This study aimed to validate a previously developed urinary methylation marker panel containing
GHSR
and
MAL
.
Methods
We enrolled 134 patients who underwent cystoscopy because of hematuria, including 63 individuals with primary bladder cancer and 71 with non-malignant findings. Urine samples were self-collected at home and sent via regular mail. Subsequently, DNA was extracted and the hypermethylation of
GHSR
and
MAL
was evaluated using quantitative methylation-specific polymerase chain reaction. The performance of methylation markers was assessed using area-under-the-curve (AUC) analysis and sensitivity and specificity based on pre-established cut-off values.
Results
Validation of the marker panel
GHSR/MAL
resulted in an AUC of 0.87 at 79% sensitivity and 80% specificity. Sensitivity was comparable to the previous investigation (
P
> 0.9), though specificity was significantly lower (
P
= 0.026). Sensitivity was higher for high-grade tumors compared to low-grade tumors (94% vs. 60%,
P
= 0.002).
Conclusion
Validation of the
GHSR/MAL
methylation marker panel on at home collected urine samples confirms its robust performance for bladder cancer detection in a hematuria population, and underscores the diagnostic potential for future clinical application. |
| doi_str_mv | 10.1007/s00345-024-05287-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11485176</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3117174569</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-ca3d6af8d6ef1fd8d7d824be2d26ccfa7026202ddd70b154a3c8c4de9715850b3</originalsourceid><addsrcrecordid>eNp9kUtLxDAUhYMoPkb_gAspuHFTvXk1GTeigzrCiOBjHdIk1Wqn1aQV-u-NU98LVzfkfPfk3hyEtjHsYwBxEAAo4ykQlgInUqR8Ca1jRmkqBcmWf5zX0EYIjwBYZMBX0RodM0w4Y-vo9qTS1jqfTHRtYrGudaYtmzrJ-6TzZa19n8xd-9BXenE91_7J-ZCcT2-uDy6PZ4eJTl51VdpBDm1n-020UugquK2POkJ3Z6e3k2k6uzq_mBzPUkN51qZGU5vpQtrMFbiw0gorCcsdsSQzptACSEaAWGsF5JgzTY00zLqxwFxyyOkIHQ2-z10-d9a4uvW6Us--jFP2qtGl-q3U5YO6b14Vxkzy-BnRYe_DwTcvnQutmpfBuKrStWu6oCjGAiRQ-o7u_kEfm87Xcb8FhQXj2ThSZKCMb0LwrviaBoN6T00NqamYmlqkpnhs2vm5x1fLZ0wRoAMQolTfO__99j-2b-Cjo1Y</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3117174569</pqid></control><display><type>article</type><title>Bladder Cancer detection by urinary methylation markers GHSR/MAL: a validation study</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Beijert, I. J. ; van den Burgt, Y. ; Hentschel, A. E. ; Bosschieter, J. ; Kauer, P. C. ; Lissenberg-Witte, B. I. ; van Moorselaar, R. J.A. ; Nieuwenhuijzen, J. A. ; Steenbergen, R. D.M.</creator><creatorcontrib>Beijert, I. J. ; van den Burgt, Y. ; Hentschel, A. E. ; Bosschieter, J. ; Kauer, P. C. ; Lissenberg-Witte, B. I. ; van Moorselaar, R. J.A. ; Nieuwenhuijzen, J. A. ; Steenbergen, R. D.M.</creatorcontrib><description>Purpose
Although cystoscopy is a reliable tool for detecting bladder cancer, it poses a high burden on patients and entails high costs. This highlights the need for non-invasive and cost-effective alternatives. This study aimed to validate a previously developed urinary methylation marker panel containing
GHSR
and
MAL
.
Methods
We enrolled 134 patients who underwent cystoscopy because of hematuria, including 63 individuals with primary bladder cancer and 71 with non-malignant findings. Urine samples were self-collected at home and sent via regular mail. Subsequently, DNA was extracted and the hypermethylation of
GHSR
and
MAL
was evaluated using quantitative methylation-specific polymerase chain reaction. The performance of methylation markers was assessed using area-under-the-curve (AUC) analysis and sensitivity and specificity based on pre-established cut-off values.
Results
Validation of the marker panel
GHSR/MAL
resulted in an AUC of 0.87 at 79% sensitivity and 80% specificity. Sensitivity was comparable to the previous investigation (
P
> 0.9), though specificity was significantly lower (
P
= 0.026). Sensitivity was higher for high-grade tumors compared to low-grade tumors (94% vs. 60%,
P
= 0.002).
Conclusion
Validation of the
GHSR/MAL
methylation marker panel on at home collected urine samples confirms its robust performance for bladder cancer detection in a hematuria population, and underscores the diagnostic potential for future clinical application.</description><identifier>ISSN: 1433-8726</identifier><identifier>ISSN: 0724-4983</identifier><identifier>EISSN: 1433-8726</identifier><identifier>DOI: 10.1007/s00345-024-05287-5</identifier><identifier>PMID: 39412544</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Aged ; Aged, 80 and over ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - urine ; Bladder cancer ; DNA Methylation ; Female ; Hematuria ; Humans ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; MutL Protein Homolog 1 - genetics ; Nephrology ; Oncology ; Receptors, Ghrelin - genetics ; Sensitivity and Specificity ; Tumors ; Urinary Bladder Neoplasms - diagnosis ; Urinary Bladder Neoplasms - genetics ; Urinary Bladder Neoplasms - urine ; Urology</subject><ispartof>World journal of urology, 2024-10, Vol.42 (1), p.578, Article 578</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>Copyright Springer Nature B.V. Dec 2024</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c356t-ca3d6af8d6ef1fd8d7d824be2d26ccfa7026202ddd70b154a3c8c4de9715850b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00345-024-05287-5$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00345-024-05287-5$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39412544$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Beijert, I. J.</creatorcontrib><creatorcontrib>van den Burgt, Y.</creatorcontrib><creatorcontrib>Hentschel, A. E.</creatorcontrib><creatorcontrib>Bosschieter, J.</creatorcontrib><creatorcontrib>Kauer, P. C.</creatorcontrib><creatorcontrib>Lissenberg-Witte, B. I.</creatorcontrib><creatorcontrib>van Moorselaar, R. J.A.</creatorcontrib><creatorcontrib>Nieuwenhuijzen, J. A.</creatorcontrib><creatorcontrib>Steenbergen, R. D.M.</creatorcontrib><title>Bladder Cancer detection by urinary methylation markers GHSR/MAL: a validation study</title><title>World journal of urology</title><addtitle>World J Urol</addtitle><addtitle>World J Urol</addtitle><description>Purpose
Although cystoscopy is a reliable tool for detecting bladder cancer, it poses a high burden on patients and entails high costs. This highlights the need for non-invasive and cost-effective alternatives. This study aimed to validate a previously developed urinary methylation marker panel containing
GHSR
and
MAL
.
Methods
We enrolled 134 patients who underwent cystoscopy because of hematuria, including 63 individuals with primary bladder cancer and 71 with non-malignant findings. Urine samples were self-collected at home and sent via regular mail. Subsequently, DNA was extracted and the hypermethylation of
GHSR
and
MAL
was evaluated using quantitative methylation-specific polymerase chain reaction. The performance of methylation markers was assessed using area-under-the-curve (AUC) analysis and sensitivity and specificity based on pre-established cut-off values.
Results
Validation of the marker panel
GHSR/MAL
resulted in an AUC of 0.87 at 79% sensitivity and 80% specificity. Sensitivity was comparable to the previous investigation (
P
> 0.9), though specificity was significantly lower (
P
= 0.026). Sensitivity was higher for high-grade tumors compared to low-grade tumors (94% vs. 60%,
P
= 0.002).
Conclusion
Validation of the
GHSR/MAL
methylation marker panel on at home collected urine samples confirms its robust performance for bladder cancer detection in a hematuria population, and underscores the diagnostic potential for future clinical application.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - urine</subject><subject>Bladder cancer</subject><subject>DNA Methylation</subject><subject>Female</subject><subject>Hematuria</subject><subject>Humans</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>MutL Protein Homolog 1 - genetics</subject><subject>Nephrology</subject><subject>Oncology</subject><subject>Receptors, Ghrelin - genetics</subject><subject>Sensitivity and Specificity</subject><subject>Tumors</subject><subject>Urinary Bladder Neoplasms - diagnosis</subject><subject>Urinary Bladder Neoplasms - genetics</subject><subject>Urinary Bladder Neoplasms - urine</subject><subject>Urology</subject><issn>1433-8726</issn><issn>0724-4983</issn><issn>1433-8726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kUtLxDAUhYMoPkb_gAspuHFTvXk1GTeigzrCiOBjHdIk1Wqn1aQV-u-NU98LVzfkfPfk3hyEtjHsYwBxEAAo4ykQlgInUqR8Ca1jRmkqBcmWf5zX0EYIjwBYZMBX0RodM0w4Y-vo9qTS1jqfTHRtYrGudaYtmzrJ-6TzZa19n8xd-9BXenE91_7J-ZCcT2-uDy6PZ4eJTl51VdpBDm1n-020UugquK2POkJ3Z6e3k2k6uzq_mBzPUkN51qZGU5vpQtrMFbiw0gorCcsdsSQzptACSEaAWGsF5JgzTY00zLqxwFxyyOkIHQ2-z10-d9a4uvW6Us--jFP2qtGl-q3U5YO6b14Vxkzy-BnRYe_DwTcvnQutmpfBuKrStWu6oCjGAiRQ-o7u_kEfm87Xcb8FhQXj2ThSZKCMb0LwrviaBoN6T00NqamYmlqkpnhs2vm5x1fLZ0wRoAMQolTfO__99j-2b-Cjo1Y</recordid><startdate>20241016</startdate><enddate>20241016</enddate><creator>Beijert, I. J.</creator><creator>van den Burgt, Y.</creator><creator>Hentschel, A. E.</creator><creator>Bosschieter, J.</creator><creator>Kauer, P. C.</creator><creator>Lissenberg-Witte, B. I.</creator><creator>van Moorselaar, R. J.A.</creator><creator>Nieuwenhuijzen, J. A.</creator><creator>Steenbergen, R. D.M.</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20241016</creationdate><title>Bladder Cancer detection by urinary methylation markers GHSR/MAL: a validation study</title><author>Beijert, I. J. ; van den Burgt, Y. ; Hentschel, A. E. ; Bosschieter, J. ; Kauer, P. C. ; Lissenberg-Witte, B. I. ; van Moorselaar, R. J.A. ; Nieuwenhuijzen, J. A. ; Steenbergen, R. D.M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-ca3d6af8d6ef1fd8d7d824be2d26ccfa7026202ddd70b154a3c8c4de9715850b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - urine</topic><topic>Bladder cancer</topic><topic>DNA Methylation</topic><topic>Female</topic><topic>Hematuria</topic><topic>Humans</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>MutL Protein Homolog 1 - genetics</topic><topic>Nephrology</topic><topic>Oncology</topic><topic>Receptors, Ghrelin - genetics</topic><topic>Sensitivity and Specificity</topic><topic>Tumors</topic><topic>Urinary Bladder Neoplasms - diagnosis</topic><topic>Urinary Bladder Neoplasms - genetics</topic><topic>Urinary Bladder Neoplasms - urine</topic><topic>Urology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beijert, I. J.</creatorcontrib><creatorcontrib>van den Burgt, Y.</creatorcontrib><creatorcontrib>Hentschel, A. E.</creatorcontrib><creatorcontrib>Bosschieter, J.</creatorcontrib><creatorcontrib>Kauer, P. C.</creatorcontrib><creatorcontrib>Lissenberg-Witte, B. I.</creatorcontrib><creatorcontrib>van Moorselaar, R. J.A.</creatorcontrib><creatorcontrib>Nieuwenhuijzen, J. A.</creatorcontrib><creatorcontrib>Steenbergen, R. D.M.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>World journal of urology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beijert, I. J.</au><au>van den Burgt, Y.</au><au>Hentschel, A. E.</au><au>Bosschieter, J.</au><au>Kauer, P. C.</au><au>Lissenberg-Witte, B. I.</au><au>van Moorselaar, R. J.A.</au><au>Nieuwenhuijzen, J. A.</au><au>Steenbergen, R. D.M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bladder Cancer detection by urinary methylation markers GHSR/MAL: a validation study</atitle><jtitle>World journal of urology</jtitle><stitle>World J Urol</stitle><addtitle>World J Urol</addtitle><date>2024-10-16</date><risdate>2024</risdate><volume>42</volume><issue>1</issue><spage>578</spage><pages>578-</pages><artnum>578</artnum><issn>1433-8726</issn><issn>0724-4983</issn><eissn>1433-8726</eissn><abstract>Purpose
Although cystoscopy is a reliable tool for detecting bladder cancer, it poses a high burden on patients and entails high costs. This highlights the need for non-invasive and cost-effective alternatives. This study aimed to validate a previously developed urinary methylation marker panel containing
GHSR
and
MAL
.
Methods
We enrolled 134 patients who underwent cystoscopy because of hematuria, including 63 individuals with primary bladder cancer and 71 with non-malignant findings. Urine samples were self-collected at home and sent via regular mail. Subsequently, DNA was extracted and the hypermethylation of
GHSR
and
MAL
was evaluated using quantitative methylation-specific polymerase chain reaction. The performance of methylation markers was assessed using area-under-the-curve (AUC) analysis and sensitivity and specificity based on pre-established cut-off values.
Results
Validation of the marker panel
GHSR/MAL
resulted in an AUC of 0.87 at 79% sensitivity and 80% specificity. Sensitivity was comparable to the previous investigation (
P
> 0.9), though specificity was significantly lower (
P
= 0.026). Sensitivity was higher for high-grade tumors compared to low-grade tumors (94% vs. 60%,
P
= 0.002).
Conclusion
Validation of the
GHSR/MAL
methylation marker panel on at home collected urine samples confirms its robust performance for bladder cancer detection in a hematuria population, and underscores the diagnostic potential for future clinical application.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>39412544</pmid><doi>10.1007/s00345-024-05287-5</doi><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Aged Aged, 80 and over Biomarkers, Tumor - genetics Biomarkers, Tumor - urine Bladder cancer DNA Methylation Female Hematuria Humans Male Medicine Medicine & Public Health Middle Aged MutL Protein Homolog 1 - genetics Nephrology Oncology Receptors, Ghrelin - genetics Sensitivity and Specificity Tumors Urinary Bladder Neoplasms - diagnosis Urinary Bladder Neoplasms - genetics Urinary Bladder Neoplasms - urine Urology |
| title | Bladder Cancer detection by urinary methylation markers GHSR/MAL: a validation study |
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