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Genomic alterations, DNA methylation, and histone modifications were analyzed using TCGA, UALCAN, ASD MethSurv, SMART, and DepMap databases. Associations with clinical outcomes, immune infiltration, and drug sensitivity were investigated through TCGA, CIBERSORT, TISIDB, single\u2010cell and spatial transcriptomics, and RNAactDrug platforms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that\n                      <jats:italic>CTSV<\/jats:italic>\n                      was upregulated in BC, especially in non\u2010papillary tumors. Moreover, its expression correlated positively with tumor grade, the presence of distant and lymph node metastases, resistance to therapy, and poorer overall and progression\u2010free survival. Furthermore,\n                      <jats:italic>CTSV<\/jats:italic>\n                      expression was associated with mutations in known BC driver genes (\n                      <jats:italic>TP53<\/jats:italic>\n                      ,\n                      <jats:italic>RB1<\/jats:italic>\n                      , and\n                      <jats:italic>ERBB2<\/jats:italic>\n                      ) and showed a correlation with promoter hypomethylation, gene body methylation, and histone markers (e.g., H3K18ac1K23ac0), suggesting an epigenetic mechanism driving\n                      <jats:italic>CTSV<\/jats:italic>\n                      expression. The\n                      <jats:italic>CTSV<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>high<\/jats:italic>\n                      <\/jats:sup>\n                      and\n                      <jats:italic>CTSV<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>low<\/jats:italic>\n                      <\/jats:sup>\n                      groups exhibited a different stromal composition, with the former showing a more immunogenic signature. Finally, we found that cell lines and tumors highly expressing\n                      <jats:italic>CTSV<\/jats:italic>\n                      exhibit higher sensitivity to multiple chemotherapeutic drugs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>CTSV<\/jats:italic>\n                      overexpression is associated with bladder cancer aggressiveness through epigenetic regulation and immune modulation, emerging as a promising prognostic biomarker and noninvasive diagnostic target.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iju.70609","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:46:28Z","timestamp":1787805988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cathepsin V (\n                    <scp>\n                      <i>CTSV<\/i>\n                    <\/scp>\n                    ) Shapes the Epigenetic\u2013Immune Landscape of Bladder Cancer and Emerges as a Noninvasive Biomarker"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9645-2292","authenticated-orcid":false,"given":"Wallax Augusto Silva","family":"Ferreira","sequence":"first","affiliation":[{"name":"Laboratory of Cytogenomics and Environmental Mutagenesis, Environment Section (SEAMB) Evandro Chagas Institute (IEC)  Ananindeua PA Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio Albuquerque","family":"Marchi","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery University of S\u00e3o Paulo Medical School  S\u00e3o Paulo SP Brazil"},{"name":"Center for Translational Research in Oncology Cancer Institute of the State of S\u00e3o Paulo (ICESP)  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glauco Akelinghton Freire","family":"Vitiello","sequence":"additional","affiliation":[{"name":"Laboratory of DNA Polymorphisms and Immunology, Department of Pathological Sciences, Biological Sciences Center Londrina State University (UEL)  Londrina PR Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3851-2696","authenticated-orcid":false,"given":"Rolando Andr\u00e9 Rios","family":"Villacis","sequence":"additional","affiliation":[{"name":"Department of Genetics and Morphology, Institute of Biological Sciences University of Bras\u00edlia (UnB)  Bras\u00edlia DF Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Paula Drummond","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Multiuser Cellular Biology and Ultrastructure Laboratory, Section of Hepatology Evandro Chagas Institute (IEC)  Bel\u00e9m PA Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edivaldo Herculano Correa de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Cytogenomics and Environmental Mutagenesis, Environment Section (SEAMB) Evandro Chagas Institute (IEC)  Ananindeua PA Brazil"},{"name":"Institute of Exact and Natural Sciences, Faculty of Natural Sciences Federal University of Par\u00e1 (UFPA)  Bel\u00e9m PA Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00744-3"},{"key":"e_1_2_11_3_1","unstructured":"S. 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