Diagnostic DNA Methylation Biomarkers for Renal Cell Carcinoma: A Systematic Review
The 5-yr survival of early-stage renal cell carcinoma (RCC) is approximately 93%, but once metastasised, the 5-yr survival plummets to 12%, indicating that early RCC detection is crucial to improvement in survival. DNA methylation biomarkers have been suggested to be of potential diagnostic value; h...
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| Veröffentlicht in: | European urology oncology 2021-04, Vol.4 (2), p.215-226 |
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| creator | Lommen, Kim Vaes, Nathalie Aarts, Maureen J. van Roermund, Joep G. Schouten, Leo J. Oosterwijk, Egbert Melotte, Veerle Tjan-Heijnen, Vivianne C. van Engeland, Manon Smits, Kim M. |
| description | The 5-yr survival of early-stage renal cell carcinoma (RCC) is approximately 93%, but once metastasised, the 5-yr survival plummets to 12%, indicating that early RCC detection is crucial to improvement in survival. DNA methylation biomarkers have been suggested to be of potential diagnostic value; however, their current state of clinical translation is unclear and a comprehensive overview is lacking.
To systematically review and summarise all literature regarding diagnostic DNA methylation biomarkers for RCC.
We performed a systematic literature review of PubMed, EMBASE, Medline, and Google Scholar up to January 2019, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. Included studies were scored according to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forest plots were generated to summarise diagnostic performance of all biomarkers. Level of evidence (LoE) and potential risk of bias were determined for all included studies.
After selection, 19 articles reporting on 44 diagnostic DNA methylation biomarkers and 11 multimarker panels were included; however, only 15 biomarkers were independently validated. STARD scores varied from 4 to 13 out of 23 points, with a median of 10 points. Large variation in subgroups, methods, and primer locations was observed. None of the reported biomarkers exceeded LoE III, and the majority of studies reported inadequately.
None of the reported biomarkers exceeded LoE III, indicating their limited clinical utility. Moreover, study reproducibility and further development of these RCC biomarkers are greatly hampered by inadequate reporting.
In this report, we reviewed whether specific biomarkers could be used to diagnose the most common form of kidney cancer. We conclude that due to limited evidence and reporting inconsistencies, none of these biomarkers can be used in clinical practice, and further development towards clinical use is hindered.
We reviewed whether DNA methylation biomarkers could be used to diagnose renal cell carcinoma. We conclude that due to limited evidence, and inadequate reporting and research methodology, none of these biomarkers are clinically useful and their further development is hampered. |
| doi_str_mv | 10.1016/j.euo.2019.07.011 |
| format | Article |
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To systematically review and summarise all literature regarding diagnostic DNA methylation biomarkers for RCC.
We performed a systematic literature review of PubMed, EMBASE, Medline, and Google Scholar up to January 2019, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. Included studies were scored according to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forest plots were generated to summarise diagnostic performance of all biomarkers. Level of evidence (LoE) and potential risk of bias were determined for all included studies.
After selection, 19 articles reporting on 44 diagnostic DNA methylation biomarkers and 11 multimarker panels were included; however, only 15 biomarkers were independently validated. STARD scores varied from 4 to 13 out of 23 points, with a median of 10 points. Large variation in subgroups, methods, and primer locations was observed. None of the reported biomarkers exceeded LoE III, and the majority of studies reported inadequately.
None of the reported biomarkers exceeded LoE III, indicating their limited clinical utility. Moreover, study reproducibility and further development of these RCC biomarkers are greatly hampered by inadequate reporting.
In this report, we reviewed whether specific biomarkers could be used to diagnose the most common form of kidney cancer. We conclude that due to limited evidence and reporting inconsistencies, none of these biomarkers can be used in clinical practice, and further development towards clinical use is hindered.
We reviewed whether DNA methylation biomarkers could be used to diagnose renal cell carcinoma. We conclude that due to limited evidence, and inadequate reporting and research methodology, none of these biomarkers are clinically useful and their further development is hampered.</description><identifier>ISSN: 2588-9311</identifier><identifier>EISSN: 2588-9311</identifier><identifier>DOI: 10.1016/j.euo.2019.07.011</identifier><identifier>PMID: 31402218</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Biomarkers ; Carcinoma, Renal Cell - diagnosis ; Carcinoma, Renal Cell - genetics ; Diagnosis ; Diagnostic Tests, Routine ; DNA Methylation ; Humans ; Kidney cancer ; Kidney Neoplasms - diagnosis ; Kidney Neoplasms - genetics ; Promoter CpG island methylation ; Renal cell carcinoma ; Reproducibility of Results</subject><ispartof>European urology oncology, 2021-04, Vol.4 (2), p.215-226</ispartof><rights>2019 The Authors</rights><rights>Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-dd5f06f42698334ba385ccd1ad3597ea3e5c70c331c17600799d5300d343e8ca3</citedby><cites>FETCH-LOGICAL-c396t-dd5f06f42698334ba385ccd1ad3597ea3e5c70c331c17600799d5300d343e8ca3</cites><orcidid>0000-0001-9571-3449</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31402218$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lommen, Kim</creatorcontrib><creatorcontrib>Vaes, Nathalie</creatorcontrib><creatorcontrib>Aarts, Maureen J.</creatorcontrib><creatorcontrib>van Roermund, Joep G.</creatorcontrib><creatorcontrib>Schouten, Leo J.</creatorcontrib><creatorcontrib>Oosterwijk, Egbert</creatorcontrib><creatorcontrib>Melotte, Veerle</creatorcontrib><creatorcontrib>Tjan-Heijnen, Vivianne C.</creatorcontrib><creatorcontrib>van Engeland, Manon</creatorcontrib><creatorcontrib>Smits, Kim M.</creatorcontrib><title>Diagnostic DNA Methylation Biomarkers for Renal Cell Carcinoma: A Systematic Review</title><title>European urology oncology</title><addtitle>Eur Urol Oncol</addtitle><description>The 5-yr survival of early-stage renal cell carcinoma (RCC) is approximately 93%, but once metastasised, the 5-yr survival plummets to 12%, indicating that early RCC detection is crucial to improvement in survival. DNA methylation biomarkers have been suggested to be of potential diagnostic value; however, their current state of clinical translation is unclear and a comprehensive overview is lacking.
To systematically review and summarise all literature regarding diagnostic DNA methylation biomarkers for RCC.
We performed a systematic literature review of PubMed, EMBASE, Medline, and Google Scholar up to January 2019, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. Included studies were scored according to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forest plots were generated to summarise diagnostic performance of all biomarkers. Level of evidence (LoE) and potential risk of bias were determined for all included studies.
After selection, 19 articles reporting on 44 diagnostic DNA methylation biomarkers and 11 multimarker panels were included; however, only 15 biomarkers were independently validated. STARD scores varied from 4 to 13 out of 23 points, with a median of 10 points. Large variation in subgroups, methods, and primer locations was observed. None of the reported biomarkers exceeded LoE III, and the majority of studies reported inadequately.
None of the reported biomarkers exceeded LoE III, indicating their limited clinical utility. Moreover, study reproducibility and further development of these RCC biomarkers are greatly hampered by inadequate reporting.
In this report, we reviewed whether specific biomarkers could be used to diagnose the most common form of kidney cancer. We conclude that due to limited evidence and reporting inconsistencies, none of these biomarkers can be used in clinical practice, and further development towards clinical use is hindered.
We reviewed whether DNA methylation biomarkers could be used to diagnose renal cell carcinoma. We conclude that due to limited evidence, and inadequate reporting and research methodology, none of these biomarkers are clinically useful and their further development is hampered.</description><subject>Biomarkers</subject><subject>Carcinoma, Renal Cell - diagnosis</subject><subject>Carcinoma, Renal Cell - genetics</subject><subject>Diagnosis</subject><subject>Diagnostic Tests, Routine</subject><subject>DNA Methylation</subject><subject>Humans</subject><subject>Kidney cancer</subject><subject>Kidney Neoplasms - diagnosis</subject><subject>Kidney Neoplasms - genetics</subject><subject>Promoter CpG island methylation</subject><subject>Renal cell carcinoma</subject><subject>Reproducibility of Results</subject><issn>2588-9311</issn><issn>2588-9311</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEtLAzEUhYMoVmp_gBuZpZuON8k8dVVbX1AVWl2HNLmjqdNJTaZK_70preJKAsmFnHO45yPkhEJMgWbn8xhXNmZAyxjyGCjdI0csLYp-ySnd_zN3SM_7OQCwcCiwQ9LhNAHGaHFEpiMjXxvrW6Oi0eMgesD2bV3L1tgmujJ2Id07Oh9V1kUTbGQdDbEOl3TKNOH3IhpE07VvcSE3CRP8NPh1TA4qWXvs7d4uebm5fh7e9cdPt_fDwbiveJm1fa3TCrIqYVlZcJ7MJC9SpTSVmqdljpJjqnJQnFNF8wwgL0udcgDNE46FkrxLzra5S2c_VuhbsTBehf1kg3blBWN5KFlmrAhSupUqZ713WImlM6HcWlAQG5xiLgJOscEpIBcBZ_Cc7uJXswXqX8cPvCC43AowlAzFnfDKYKNQG4eqFdqaf-K_AeQ4g7g</recordid><startdate>202104</startdate><enddate>202104</enddate><creator>Lommen, Kim</creator><creator>Vaes, Nathalie</creator><creator>Aarts, Maureen J.</creator><creator>van Roermund, Joep G.</creator><creator>Schouten, Leo J.</creator><creator>Oosterwijk, Egbert</creator><creator>Melotte, Veerle</creator><creator>Tjan-Heijnen, Vivianne C.</creator><creator>van Engeland, Manon</creator><creator>Smits, Kim M.</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><orcidid>https://orcid.org/0000-0001-9571-3449</orcidid></search><sort><creationdate>202104</creationdate><title>Diagnostic DNA Methylation Biomarkers for Renal Cell Carcinoma: A Systematic Review</title><author>Lommen, Kim ; Vaes, Nathalie ; Aarts, Maureen J. ; van Roermund, Joep G. ; Schouten, Leo J. ; Oosterwijk, Egbert ; Melotte, Veerle ; Tjan-Heijnen, Vivianne C. ; van Engeland, Manon ; Smits, Kim M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-dd5f06f42698334ba385ccd1ad3597ea3e5c70c331c17600799d5300d343e8ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Biomarkers</topic><topic>Carcinoma, Renal Cell - diagnosis</topic><topic>Carcinoma, Renal Cell - genetics</topic><topic>Diagnosis</topic><topic>Diagnostic Tests, Routine</topic><topic>DNA Methylation</topic><topic>Humans</topic><topic>Kidney cancer</topic><topic>Kidney Neoplasms - diagnosis</topic><topic>Kidney Neoplasms - genetics</topic><topic>Promoter CpG island methylation</topic><topic>Renal cell carcinoma</topic><topic>Reproducibility of Results</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lommen, Kim</creatorcontrib><creatorcontrib>Vaes, Nathalie</creatorcontrib><creatorcontrib>Aarts, Maureen J.</creatorcontrib><creatorcontrib>van Roermund, Joep G.</creatorcontrib><creatorcontrib>Schouten, Leo J.</creatorcontrib><creatorcontrib>Oosterwijk, Egbert</creatorcontrib><creatorcontrib>Melotte, Veerle</creatorcontrib><creatorcontrib>Tjan-Heijnen, Vivianne C.</creatorcontrib><creatorcontrib>van Engeland, Manon</creatorcontrib><creatorcontrib>Smits, Kim M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European urology oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lommen, Kim</au><au>Vaes, Nathalie</au><au>Aarts, Maureen J.</au><au>van Roermund, Joep G.</au><au>Schouten, Leo J.</au><au>Oosterwijk, Egbert</au><au>Melotte, Veerle</au><au>Tjan-Heijnen, Vivianne C.</au><au>van Engeland, Manon</au><au>Smits, Kim M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diagnostic DNA Methylation Biomarkers for Renal Cell Carcinoma: A Systematic Review</atitle><jtitle>European urology oncology</jtitle><addtitle>Eur Urol Oncol</addtitle><date>2021-04</date><risdate>2021</risdate><volume>4</volume><issue>2</issue><spage>215</spage><epage>226</epage><pages>215-226</pages><issn>2588-9311</issn><eissn>2588-9311</eissn><abstract>The 5-yr survival of early-stage renal cell carcinoma (RCC) is approximately 93%, but once metastasised, the 5-yr survival plummets to 12%, indicating that early RCC detection is crucial to improvement in survival. DNA methylation biomarkers have been suggested to be of potential diagnostic value; however, their current state of clinical translation is unclear and a comprehensive overview is lacking.
To systematically review and summarise all literature regarding diagnostic DNA methylation biomarkers for RCC.
We performed a systematic literature review of PubMed, EMBASE, Medline, and Google Scholar up to January 2019, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines. Included studies were scored according to the Standards for Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forest plots were generated to summarise diagnostic performance of all biomarkers. Level of evidence (LoE) and potential risk of bias were determined for all included studies.
After selection, 19 articles reporting on 44 diagnostic DNA methylation biomarkers and 11 multimarker panels were included; however, only 15 biomarkers were independently validated. STARD scores varied from 4 to 13 out of 23 points, with a median of 10 points. Large variation in subgroups, methods, and primer locations was observed. None of the reported biomarkers exceeded LoE III, and the majority of studies reported inadequately.
None of the reported biomarkers exceeded LoE III, indicating their limited clinical utility. Moreover, study reproducibility and further development of these RCC biomarkers are greatly hampered by inadequate reporting.
In this report, we reviewed whether specific biomarkers could be used to diagnose the most common form of kidney cancer. We conclude that due to limited evidence and reporting inconsistencies, none of these biomarkers can be used in clinical practice, and further development towards clinical use is hindered.
We reviewed whether DNA methylation biomarkers could be used to diagnose renal cell carcinoma. We conclude that due to limited evidence, and inadequate reporting and research methodology, none of these biomarkers are clinically useful and their further development is hampered.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>31402218</pmid><doi>10.1016/j.euo.2019.07.011</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-9571-3449</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Biomarkers Carcinoma, Renal Cell - diagnosis Carcinoma, Renal Cell - genetics Diagnosis Diagnostic Tests, Routine DNA Methylation Humans Kidney cancer Kidney Neoplasms - diagnosis Kidney Neoplasms - genetics Promoter CpG island methylation Renal cell carcinoma Reproducibility of Results |
| title | Diagnostic DNA Methylation Biomarkers for Renal Cell Carcinoma: A Systematic Review |
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