{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:34:59Z","timestamp":1760060099597,"version":"build-2065373602"},"reference-count":81,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III (ISCIII)","doi-asserted-by":"publisher","award":["PI22\/00025","CNS2024-154855"],"award-info":[{"award-number":["PI22\/00025","CNS2024-154855"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science, Innovation, and Universities","doi-asserted-by":"publisher","award":["PI22\/00025","CNS2024-154855"],"award-info":[{"award-number":["PI22\/00025","CNS2024-154855"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mitomycin C (MMC) is a widely employed chemotherapeutic agent, particularly in non-muscle invasive bladder cancer (NMIBC), where it functions by inducing DNA cross-linking and promoting tumor cell apoptosis. However, the tumor microenvironment (TME) significantly influences the therapeutic efficacy of MMC. Among the key regulators within the TME, the complement system and the coagulation pathway play a crucial role in modulating immune responses to cancer therapies, including MMC. This article explores the interaction between platinum nanoparticles (PtNPs) with human serum (HS) of NMIBC patients (T1 and Ta subtypes) at three different points: before the chemotherapy instillation of MMC (t0) and three (t3) and six months (t6) after the treatment with MMC. This novel nanoproteomic strategy allowed the identification of a TME proteomic signature associated with the response to MMC treatment. Importantly, two proteins involved in the immune response were found to be deregulated across all patients (T1 and Ta subtypes) during MMC treatment: prothrombin (F2) downregulated and complement component C7 (C7) upregulated. By understanding how these biomarker proteins interact with MMC treatment, novel therapeutic strategies can be developed to enhance treatment outcomes and overcome resistance in NMIBC.<\/jats:p>","DOI":"10.3390\/ijms26157413","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T15:56:16Z","timestamp":1754409376000},"page":"7413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Variations in Circulating Tumor Microenvironment-Associated Proteins in Non-Muscle Invasive Bladder Cancer Induced by Mitomycin C Treatment"],"prefix":"10.3390","volume":"26","author":[{"given":"Benito Blanco","family":"G\u00f3mez","sequence":"first","affiliation":[{"name":"Urology Division, Lucus Augusti University Hospital (HULA), Servizo Galego de Sa\u00fade (SERGAS), 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco Javier","family":"Casas-Nebra","sequence":"additional","affiliation":[{"name":"Urology Division, Lucus Augusti University Hospital (HULA), Servizo Galego de Sa\u00fade (SERGAS), 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6348-8646","authenticated-orcid":false,"given":"Daniel","family":"P\u00e9rez-Fentes","sequence":"additional","affiliation":[{"name":"Urology Division, University Clinical Hospital of Santiago de Compostela (CHUS), Servizo Galego de Sa\u00fade (SERGAS), 15706 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7615-3079","authenticated-orcid":false,"given":"Susana B.","family":"Bravo","sequence":"additional","affiliation":[{"name":"Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago de Compostela (CHUS), 15706 Santiago de Compostela, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4071-3967","authenticated-orcid":false,"given":"Laura","family":"Rodr\u00edguez-Silva","sequence":"additional","affiliation":[{"name":"Inorganic Chemistry Department, Faculty of Sciences, Campus Terra, University of Santiago de Compostela, 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"N\u00fa\u00f1ez","sequence":"additional","affiliation":[{"name":"Inorganic Chemistry Department, Faculty of Sciences, Campus Terra, University of Santiago de Compostela, 27002 Lugo, Spain"},{"name":"Research Unit, Hospital Universitario Lucus Augusti (HULA), Servizo Galego de Sa\u00fade (SERGAS), 27002 Lugo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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