Extracellular vesicles expressing CEACAM proteins in the urine of bladder cancer patients. Issue 9 (27th June 2022)

• Record Type: Journal Article
• Authors: Igami, Ko; Uchiumi, Takeshi; Shiota, Masaki; Ueda, Saori; Tsukahara, Shigehiro; Akimoto, Masaru; Eto, Masatoshi; Kang, Dongchon
• Is Part Of: Cancer science. Volume 113:Issue 9(2022)
• Page Start: 3120
• Page End: 3133
• Publication Date: 2022-06-27
• Subjects: bladder cancer -- CEACAM -- extracellular vesicle -- flow cytometry -- proteomics; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.15438
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Early detection and long‐term monitoring are important for urothelial carcinoma of the bladder (UCB). Urine cytology and existing markers have insufficient diagnostic performance. Here, we examined medium‐sized extracellular vesicles (EVs) in urine to identify specific markers for UCB and evaluated their usefulness as diagnostic material. To identify specific markers in urinary EVs derived from UCB, we undertook shotgun proteomics using urine from four UCB patients and four healthy subjects. Next, 29 healthy specimens, 18 noncancer specimens, and 33 UCB specimens, all from men, were analyzed for urinary EVs by flow cytometry to evaluate the diagnostic performance of UCB‐specific EVs. Nanoparticle‐tracking analysis indicated that the size of EVs extracted from urine was mostly <400 nm. By shotgun proteomics, we detected several proteins characteristic of UCB and found that carcinoembryonic antigen‐related adhesion molecule (CEACAM) proteins were increased in patients. Flow cytometric analysis revealed that the degree of expression of CEACAM1, CEACAM5, and CEACAM6 proteins on the surface of EVs varied among patients. Extracellular vesicles expressing CEACAM proteins also expressed mucin 1, suggesting that they were derived from tumorigenic uroepithelial cells. The number of EVs expressing CEACAM1, 5, and 6 proteins was significantly increased in UCB (mean ± SD, 8.6 ± 13%) compared to non‐UCB (0.69 ± 0.46) and healthy (0.46 ± 0.34) by flow cytometry. The results of receiver operating characteristic (ROC) analysis showed a good score of area under the ROC curve of 0.907. We identified EVs that specifically express CEACAM proteins in urine and have potential for diagnostic applications. These EVs are potential targets in a new liquid biopsy test for UCB patients. Abstract : ・Increased CEACAM proteins was found in EV fraction of urine from patients with bladder cancer by shotgun proteomics. ・Urinary EVs expressing CEACAM proteins, characterized by flow cytometry, are also accompanied by MUC1, which is increased in patients with bladder cancer. ・EVs expressing CEACAM proteins in urine have good diagnostic performance to detect bladder cancer patients.