{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:16:52Z","timestamp":1789690612380,"version":"4.0.1"},"reference-count":25,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2014M3C9A306855423"],"award-info":[{"award-number":["2014M3C9A306855423"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1F1A1068488"],"award-info":[{"award-number":["2020R1F1A1068488"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1I1A3062508"],"award-info":[{"award-number":["2020R1I1A3062508"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Osong Medical Innovation Foundation, funded by Chungcheongbuk-do","award":["AG200904005 and AG200902001"],"award-info":[{"award-number":["AG200904005 and AG200902001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-muscle-invasive bladder cancer (NMIBC) is clinically heterogeneous; thus, many patients fail to respond to treatment and relapse. Here, we identified a molecular signature that is both prognostic and predictive for NMIBC heterogeneity and responses to Bacillus Calmette-Gu\u00e9rin (BCG) therapy. Transcriptomic profiling of 948 NMIBC patients identified a signature-based subtype predictor, MSP888, along with three distinct molecular subtypes: DP.BCG+ (related to progression and response to BCG treatment), REC.BCG+ (related to recurrence and response to BCG treatment), and EP (equivocal prognosis). Patients with the DP.BCG+ subtype showed worse progression-free survival but responded to BCG treatment, whereas those with the REC.BCG+ subtype showed worse recurrence-free survival but responded to BCG treatment. Multivariate analyses revealed that MSP888 showed independent clinical utility for predicting NMIBC prognosis (each p = 0.001 for progression and recurrence, respectively). Comparative analysis of this classifier and previously established molecular subtypes (i.e., Lund taxonomy and UROMOL class) revealed that a great proportion of patients were similar between subtypes; however, the MSP888 predictor better differentiated biological activity or responsiveness to BCG treatment. Our data increase our understanding of the mechanisms underlying the poor prognosis of NMIBC and the effectiveness of BCG therapy, which should improve clinical practice and complement other diagnostic tools.<\/jats:p>","DOI":"10.3390\/ijms22031450","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T11:40:48Z","timestamp":1612179648000},"page":"1450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Molecular Signature Determines the Prognostic and Therapeutic Subtype of Non-Muscle-Invasive Bladder Cancer Responsive to Intravesical Bacillus Calmette-Gu\u00e9rin Therapy"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4176-5187","authenticated-orcid":false,"given":"Seon-Kyu","family":"Kim","sequence":"first","affiliation":[{"name":"Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Hwan","family":"Park","sequence":"additional","affiliation":[{"name":"Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Department of Bioinformatics, KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeong Uk","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Urology, College of Medicine, Yeungnam University, Daegu 38541, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Joon","family":"Byun","sequence":"additional","affiliation":[{"name":"Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6847-7743","authenticated-orcid":false,"given":"Xuan-Mei","family":"Piao","sequence":"additional","affiliation":[{"name":"Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pildu","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea"},{"name":"Department of Urology, Chungbuk National University Hospital, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Youn","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea"},{"name":"Department of Urology, Chungbuk National University Hospital, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Pil","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea"},{"name":"Department of Urology, Chungbuk National University Hospital, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Won","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea"},{"name":"Department of Urology, Chungbuk National University Hospital, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Tae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea"},{"name":"Department of Urology, Chungbuk National University Hospital, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-June","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea"},{"name":"Department of Urology, Chungbuk National University Hospital, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Cheol","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea"},{"name":"Department of Urology, Chungbuk National University Hospital, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Kwon","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, College of Biotechnology &amp; Natural Resource, Chung-Ang University, Anseong 06974, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1454-3124","authenticated-orcid":false,"given":"Yung Hyun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Urology, Personalized Tumor Engineering Research Center, Chungbuk National University College of Medicine, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8060-8926","authenticated-orcid":false,"given":"Wun-Jae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea"},{"name":"Department of Urology, Chungbuk National University Hospital, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"},{"name":"Korea Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7737-4746","authenticated-orcid":false,"given":"Seok Joong","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Urology, Chungbuk National University College of Medicine, Cheongju 28644, Korea"},{"name":"Department of Urology, Chungbuk National University Hospital, Cheongju 28644, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"Ferlay","year":"2015","journal-title":"Int. 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