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Urinary exosomes are promising biomarkers for liquid biopsy, but urine's high variability requires normalization for accurate analysis. This study proposes using the PD\u2010L1\/Alix ratio to normalize exosomal PD\u2010L1 signal intensity with Alix, an internal exosomal protein less susceptible to heterogeneity concerns than surface protein markers. Extracellular vesicles were isolated using ExoDisc and characterized using various methods, including ExoView to analyze tetraspanins, PD\u2010L1, and Alix on individual exosomes. On\u2010disc ELISA was used to evaluate PD\u2010L1 and Alix\u2010normalized PD\u2010L1 in 15 urothelial cancer patients during the initial treatment cycle with Tecentriq. Results showed that Alix signal range was relatively uniform, whereas tetraspanin marker intensity varied for individual exosome particles. On\u2010disc ELISA was more reliable for detecting exosomal PD\u2010L1 expression than standard plate ELISA\u2010based measurement. Using exosomal Alix expression for normalization is a more reliable approach than conventional methods for monitoring patient status. Overall, the study provides a practical and reliable method for detecting exosomal PD\u2010L1 in urine samples from patients with urothelial cancer.<\/jats:p>","DOI":"10.1111\/cas.16106","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T03:11:05Z","timestamp":1710385865000},"page":"1602-1610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Alix\u2010normalized exosomal programmed death\u2010ligand 1 analysis in urine enables precision monitoring of urothelial cancer"],"prefix":"10.1111","volume":"115","author":[{"given":"Hyun\u2010Kyung","family":"Woo","sequence":"first","affiliation":[{"name":"Center for Soft and Living Matter Institute for Basic Science (IBS)  Ulsan South Korea"},{"name":"Department of Biomedical Engineering Ulsan National Institute of Science and Technology (UNIST)  Ulsan South 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