A Urine-based DNA Methylation Marker Test to Detect Upper Tract Urothelial Carcinoma: A Prospective Cohort Study

医学 膀胱癌 DNA甲基化 上尿路 泌尿科 尿 甲基化 前瞻性队列研究 尿路上皮癌 队列 肿瘤科 内科学 泌尿系统 癌症 DNA 基因 遗传学 基因表达 生物
作者
Alireza Ghoreifi,Seyedeh‐Sanam Ladi‐Seyedian,Paolo Piatti,Yap Ching Chew,Benjamin Jara,Lucy Sanossian,Jeffrey Bhasin,Taikun Yamada,Gerhard Fuchs,Sumeet Bhanvadia,René Sotelo,Andrew J. Hung,Monish Aron,Mihir Desai,Inderbir S. Gill,Siamak Daneshmand,Gangning Liang,Hooman Djaladat
出处
期刊:The Journal of Urology [Ovid Technologies (Wolters Kluwer)]
卷期号:209 (5): 854-862 被引量:11
标识
DOI:10.1097/ju.0000000000003188
摘要

No AccessJournal of UrologyAdult Urology1 May 2023A Urine-based DNA Methylation Marker Test to Detect Upper Tract Urothelial Carcinoma: A Prospective Cohort StudyThis article is commented on by the following:Editorial Comment Alireza Ghoreifi, Seyedeh-Sanam Ladi-Seyedian, Paolo Piatti, Yap Ching Chew, Benjamin Jara, Lucy Sanossian, Jeffrey M. Bhasin, Taikun Yamada, Gerhard Fuchs, Sumeet Bhanvadia, Rene Sotelo, Andrew Hung, Monish Aron, Mihir Desai, Inderbir Gill, Siamak Daneshmand, Gangning Liang, and Hooman Djaladat Alireza GhoreifiAlireza Ghoreifi https://orcid.org/0000-0002-7368-7240 Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California , Seyedeh-Sanam Ladi-SeyedianSeyedeh-Sanam Ladi-Seyedian Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California , Paolo PiattiPaolo Piatti Zymo Research Corp, Irvine, California Pangea Laboratory LLC, Tustin, California , Yap Ching ChewYap Ching Chew Zymo Research Corp, Irvine, California Pangea Laboratory LLC, Tustin, California , Benjamin JaraBenjamin Jara Pangea Laboratory LLC, Tustin, California , Lucy SanossianLucy Sanossian Pangea Laboratory LLC, Tustin, California , Jeffrey M. BhasinJeffrey M. Bhasin Zymo Research Corp, Irvine, California , Taikun YamadaTaikun Yamada Zymo Research Corp, Irvine, California Pangea Laboratory LLC, Tustin, California , Gerhard FuchsGerhard Fuchs Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California , Sumeet BhanvadiaSumeet Bhanvadia Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California , Rene SoteloRene Sotelo Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California , Andrew HungAndrew Hung Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California , Monish AronMonish Aron Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California , Mihir DesaiMihir Desai Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California , Inderbir GillInderbir Gill Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California , Siamak DaneshmandSiamak Daneshmand Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California , Gangning LiangGangning Liang Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California , and Hooman DjaladatHooman Djaladat *Correspondence: Catherine and Joseph Aresty Department of Urology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Ave, Suite 7416, Los Angeles, CA 90089 telephone: 323-865-3700, E-mail Address: [email protected] Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California View All Author Informationhttps://doi.org/10.1097/JU.0000000000003188AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We explored the accuracy of a urine-based epigenetic test for detecting upper tract urothelial carcinoma. Materials and Methods: Under an Institutional Review Board–approved protocol, urine samples were prospectively collected from primary upper tract urothelial carcinoma patients before radical nephroureterectomy, ureterectomy, or ureteroscopy between December 2019 and March 2022. Samples were analyzed with Bladder CARE, a urine-based test that measures the methylation levels of 3 cancer biomarkers (TRNA-Cys, SIM2, and NKX1-1) and 2 internal control loci using methylation-sensitive restriction enzymes coupled with quantitative polymerase chain reaction. Results were reported as the Bladder CARE Index score and quantitatively categorized as positive (>5), high risk (2.5-5), or negative (<2.5). The findings were compared with those of 1:1 sex/age-matched cancer-free healthy individuals. Results: Fifty patients (40 radical nephroureterectomy, 7 ureterectomy, and 3 ureteroscopy) with a median (IQR) age of 72 (64-79) years were included. Bladder CARE Index results were positive in 47, high risk in 1, and negative in 2 patients. A significant correlation was found between Bladder CARE Index values and tumor size. Urine cytology was available for 35 patients, of whom 22 (63%) results were false-negative. Upper tract urothelial carcinoma patients had significantly higher Bladder CARE Index values compared to the controls (mean 189.3 vs 1.6, P < .001). The sensitivity, specificity, positive predictive value, and negative predictive value of the Bladder CARE test for detecting upper tract urothelial carcinoma were 96%, 88%, 89%, and 96%, respectively. Conclusions: Bladder CARE is an accurate urine-based epigenetic test for the diagnosis of upper tract urothelial carcinoma, with much higher sensitivity than standard urine cytology. REFERENCES 1. . The incidence and prevalence of upper tract urothelial carcinoma: a systematic review. BMC Urol. 2021; 21(1):110. Crossref, Medline, Google Scholar 2. . 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Detection of urothelial carcinoma, upper tract urothelial carcinoma, bladder carcinoma, and urothelial carcinoma with gross hematuria using selected urine-DNA methylation biomarkers: a prospective, single-center study. Urol Oncol. 2018; 36(7):342.e15-342.e23. Crossref, Medline, Google Scholar 23. . Upper urothelial tract high-grade carcinoma: comparison of urine cytology and DNA methylation analysis in urinary samples. Hum Pathol. 2021; 118:42-48. Crossref, Medline, Google Scholar 24. . DNA methylation urine biomarkers test in the diagnosis of upper tract urothelial carcinoma: results from a single-center prospective clinical trial. J Urol. 2022; 208(3):570-579. Link, Google Scholar Support: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflict of Interest: PP, YCC, BJ, LS, JMB, and TY are affiliated to the Zymo Research Corp and/or Pangea Laboratory. SB reports financial interest and/or other relationship with Merck and Johnson & Johnson. Ethics Statement: This study received Institutional Review Board approval (IRB No. HS-055029). Author Contributions: Design and implementation of the research: AG, HD; data collection: AG, SSLS; analysis of samples and results: PP, YCC, BJ, LS, JMB, TY; manuscript writing: AG; critical revision of the manuscript: GF, SB, RS, AH, MA, MD, IG, SD, GL; conceived the original idea and supervised the project: GL, HD. Data Availability: The data sets generated during and/or analyzed during the current study are available from the Corresponding Author on reasonable request. © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited bySiemens D (2023) This Month in Adult UrologyJournal of Urology, VOL. 209, NO. 5, (821-822), Online publication date: 1-May-2023.Ghoreifi A, Ladi-Seyedian S, Piatti P, Chew Y, Jara B, Sanossian L, Bhasin J, Yamada T, Fuchs G, Bhanvadia S, Sotelo R, Hung A, Aron M, Desai M, Gill I, Daneshmand S, Liang G and Djaladat H (2023) Reply by AuthorsJournal of Urology, VOL. 209, NO. 5, (862-862), Online publication date: 1-May-2023.Isharwal S (2023) Editorial CommentJournal of Urology, VOL. 209, NO. 5, (861-862), Online publication date: 1-May-2023.Related articlesJournal of Urology23 Feb 2023Editorial Comment Volume 209Issue 5May 2023Page: 854-862 Peer Review Report Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.Keywordsurine specimen collectiondiagnosisDNA methylationtransitional cellbiomarkerscarcinomaMetricsAuthor Information Alireza Ghoreifi Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California More articles by this author Seyedeh-Sanam Ladi-Seyedian Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California More articles by this author Paolo Piatti Zymo Research Corp, Irvine, California Pangea Laboratory LLC, Tustin, California More articles by this author Yap Ching Chew Zymo Research Corp, Irvine, California Pangea Laboratory LLC, Tustin, California More articles by this author Benjamin Jara Pangea Laboratory LLC, Tustin, California More articles by this author Lucy Sanossian Pangea Laboratory LLC, Tustin, California More articles by this author Jeffrey M. Bhasin Zymo Research Corp, Irvine, California More articles by this author Taikun Yamada Zymo Research Corp, Irvine, California Pangea Laboratory LLC, Tustin, California More articles by this author Gerhard Fuchs Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California More articles by this author Sumeet Bhanvadia Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California More articles by this author Rene Sotelo Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California More articles by this author Andrew Hung Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California More articles by this author Monish Aron Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California More articles by this author Mihir Desai Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California More articles by this author Inderbir Gill Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California More articles by this author Siamak Daneshmand Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California More articles by this author Gangning Liang Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California More articles by this author Hooman Djaladat Catherine and Joseph Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California *Correspondence: Catherine and Joseph Aresty Department of Urology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Ave, Suite 7416, Los Angeles, CA 90089 telephone: 323-865-3700, E-mail Address: [email protected] More articles by this author Expand All Support: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflict of Interest: PP, YCC, BJ, LS, JMB, and TY are affiliated to the Zymo Research Corp and/or Pangea Laboratory. SB reports financial interest and/or other relationship with Merck and Johnson & Johnson. Ethics Statement: This study received Institutional Review Board approval (IRB No. HS-055029). Author Contributions: Design and implementation of the research: AG, HD; data collection: AG, SSLS; analysis of samples and results: PP, YCC, BJ, LS, JMB, TY; manuscript writing: AG; critical revision of the manuscript: GF, SB, RS, AH, MA, MD, IG, SD, GL; conceived the original idea and supervised the project: GL, HD. Data Availability: The data sets generated during and/or analyzed during the current study are available from the Corresponding Author on reasonable request. Advertisement PDF downloadLoading ...
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