{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:46:14Z","timestamp":1760150774880,"version":"build-2065373602"},"reference-count":71,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T00:00:00Z","timestamp":1703808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cancer Research Grant from the Pyung-Ya Foundation","award":["PY-1","HJM-TR1"],"award-info":[{"award-number":["PY-1","HJM-TR1"]}]},{"name":"Translational Research Grant from the HJM Foundation","award":["PY-1","HJM-TR1"],"award-info":[{"award-number":["PY-1","HJM-TR1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Several studies have shown that microsatellite changes can be profiled in urine for the detection of bladder cancer. The use of microsatellite analysis (MSA) for bladder cancer detection requires a comprehensive analysis of as many as 15 to 20 markers, based on the amplification and interpretations of many individual MSA markers, and it can be technically challenging. Here, to develop fast, more efficient, standardized, and less costly MSA for the detection of bladder cancer, we developed three multiplex-polymerase-chain-reaction-(PCR)-based MSA assays, all of which were analyzed via a genetic analyzer. First, we selected 16 MSA markers based on 9 selected publications. Based on samples from Johns Hopkins University (the JHU sample, the first set sample), we developed an MSA based on triplet, three-tube-based multiplex PCR (a Triplet MSA assay). The discovery, validation, and translation of biomarkers for the early detection of cancer are the primary focuses of the Early Detection Research Network (EDRN), an initiative of the National Cancer Institute (NCI). A prospective study sponsored by the EDRN was undertaken to determine the efficacy of a novel set of MSA markers for the early detection of bladder cancer. This work and data analysis were performed through a collaboration between academics and industry partners. In the current study, we undertook a re-analysis of the primary data from the Compass study to enhance the predictive power of the dataset in bladder cancer diagnosis. Using a four-stage pipeline of modern machine learning techniques, including outlier removal with a nonlinear model, correcting for majority\/minority class imbalance, feature engineering, and the use of a model-derived variable importance measure to select predictors, we were able to increase the utility of the original dataset to predict the occurrence of bladder cancer. The results of this analysis showed an increase in accuracy (85%), sensitivity (82%), and specificity (83%) compared to the original analysis. The re-analysis of the EDRN study results using machine learning statistical analysis proved to achieve an appropriate level of accuracy, sensitivity, and specificity to support the use of the MSA for bladder cancer detection and monitoring. This assay can be a significant addition to the tools urologists use to both detect primary bladder cancers and monitor recurrent bladder cancer.<\/jats:p>","DOI":"10.3390\/ijms25010472","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T09:15:11Z","timestamp":1703841311000},"page":"472","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Results Obtained from a Pivotal Validation Trial of a Microsatellite Analysis (MSA) Assay for Bladder Cancer Detection through a Statistical Approach Using a Four-Stage Pipeline of Modern Machine Learning Techniques"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1966-8877","authenticated-orcid":false,"given":"Thomas","family":"Reynolds","sequence":"first","affiliation":[{"name":"NEXT Bio-Research Services, LLC, 11601 Ironbridge Road, Suite 101, Chester, VA 23831, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Riddick","sequence":"additional","affiliation":[{"name":"NEXT Bio-Research Services, LLC, 11601 Ironbridge Road, Suite 101, Chester, VA 23831, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Meyers","sequence":"additional","affiliation":[{"name":"NEXT Bio-Research Services, LLC, 11601 Ironbridge Road, Suite 101, Chester, VA 23831, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxie","family":"Gordon","sequence":"additional","affiliation":[{"name":"HJM Cancer Research Foundation Corporation, 10606 Candlewick Road, Lutherville, MD 21093, USA"},{"name":"BCD Innovations USA, 10606 Candlewick Road, Lutherville, MD 21093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela Vanessa","family":"Flores Monar","sequence":"additional","affiliation":[{"name":"HJM Cancer Research Foundation Corporation, 10606 Candlewick Road, Lutherville, MD 21093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Moon","sequence":"additional","affiliation":[{"name":"HJM Cancer Research Foundation Corporation, 10606 Candlewick Road, Lutherville, MD 21093, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-4298","authenticated-orcid":false,"given":"Chulso","family":"Moon","sequence":"additional","affiliation":[{"name":"HJM Cancer Research Foundation Corporation, 10606 Candlewick Road, Lutherville, MD 21093, USA"},{"name":"BCD Innovations USA, 10606 Candlewick Road, Lutherville, MD 21093, USA"},{"name":"Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins Medical Institution, Cancer Research Building II, 5M3, 1550 Orleans Street, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1126\/science.8484121","article-title":"Clues to the pathogenesis of familial colorectal cancer","volume":"260","author":"Aaltonen","year":"1993","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/363558a0","article-title":"Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis","volume":"363","author":"Ionov","year":"1993","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.8484122","article-title":"Microsatellite instability in cancer of the proximal colon","volume":"260","author":"Thibodeau","year":"1993","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1093\/carcin\/bgm228","article-title":"Carcinogenesis and microsatellite instability: The interrelationship between genetics and epigenetics","volume":"29","author":"Imai","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.3748\/wjg.v18.i22.2745","article-title":"Interrelationship between microsatellite instability and microRNA in gastrointestinal cancer","volume":"18","author":"Yamamoto","year":"2012","journal-title":"World J. 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