{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:13:27Z","timestamp":1778649207380,"version":"3.51.4"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Noninvasive detection of bladder cancer remains challenging because many urine tests trade sensitivity for specificity. We evaluated whether a biologically grounded, complementary three\u2212gene methylation panel measured in urine could improve diagnostic performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a single-center 1:1 matched case-control study using clinically relevant urine samples. Urine DNA was subjected to bisulfite conversion and quantitative methylation analysis targeting three gene loci (\n                      <jats:italic>TRPS1<\/jats:italic>\n                      ,\n                      <jats:italic>HAND2<\/jats:italic>\n                      ,\n                      <jats:italic>ZNF154<\/jats:italic>\n                      ). We evaluated the performance of individual genes and a combined panel, reporting sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the receiver operating characteristic curve (AUC and ROC), and 95% confidence intervals (CI).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      One hundred and seventy-two subjects (86 cases and 86 controls) with a mean age of 60.24 \u00b1 12.54 and 59.70 \u00b1 12.75 years old were included.\n                      <jats:italic>TRPS1<\/jats:italic>\n                      showed the highest sensitivity at 0.97 with specificity 0.791, yielding PPV 0.82 and NPV 0.97;\n                      <jats:italic>HAND2<\/jats:italic>\n                      maintained strong sensitivity (0.95) but lower specificity (0.56), with PPV 0.68 and NPV 0.92; and\n                      <jats:italic>ZNF154<\/jats:italic>\n                      had sensitivity 0.93 with the lowest specificity (0.35), corresponding to PPV 0.59 and NPV 0.83.\u00a0A combined methylation assay where all three genes are methylation-positive significantly improved specificity to 0.95 while maintaining acceptable sensitivity (0.86), resulting in the highest positive predictive value (0.95) and a robust negative predictive value (0.87). The ROC analysis showed strong diagnostic performance for all three urinary methylation markers:\n                      <jats:italic>TRPS1<\/jats:italic>\n                      had the highest AUC at 0.98 (95% CI: 0.96\u20130.99), followed by\n                      <jats:italic>HAND2<\/jats:italic>\n                      at 0.90 (95% CI: 0.85\u20130.95) and\n                      <jats:italic>ZNF154<\/jats:italic>\n                      at 0.82 (95% CI: 0.76\u20130.89).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      A urine\u2212based three\u2212gene methylation panel (\n                      <jats:italic>TRPS1<\/jats:italic>\n                      ,\n                      <jats:italic>HAND2<\/jats:italic>\n                      ,\n                      <jats:italic>ZNF154<\/jats:italic>\n                      ) demonstrates promising accuracy for bladder cancer detection, with complementary signals improving specificity. Findings are constrained by a single\u2013center cohort and moderate size and require external, multi\u2212center validation in the future.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1812094","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:46:38Z","timestamp":1778647598000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Urinary DNA methylation biomarkers for bladder cancer diagnosis: a single center case-control study"],"prefix":"10.3389","volume":"16","author":[{"given":"Chao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Urology, Xiamen Haicang Hospital","place":["Xiamen, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongjin","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiamen Haicang Hospital","place":["Xiamen, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiqian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiamen Haicang Hospital","place":["Xiamen, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongchao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiamen Haicang Hospital","place":["Xiamen, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songtao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiamen Haicang Hospital","place":["Xiamen, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinglong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiamen Haicang Hospital","place":["Xiamen, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiamen Haicang Hospital","place":["Xiamen, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghuang","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Urology, Xiamen Haicang Hospital","place":["Xiamen, Fujian, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.05.079","article-title":"Urothelial carcinoma of the bladder and the upper tract: disparate twins","volume":"189","author":"Green","year":"2013","journal-title":"J Urol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 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