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A total of 51 patients diagnosed with low-grade Ta stage non-muscle-invasive bladder cancer were recruited. Paired tissue samples from tumor lesions and adjacent healthy bladder mucosa (BM) were analyzed to identify differentially expressed genes (DEGs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the top 100 most significant DEGs for each gender, overwhelmingly more upregulated in BC comparing with BM were in male than female tissues (90% vs. 19%). The most significantly altered expression in female BC tissues included\n                      <jats:italic>MT-ND6, ARL4C, ASGR1, MYBL1<\/jats:italic>\n                      , and\n                      <jats:italic>SCAMP5<\/jats:italic>\n                      , whereas in males,\n                      <jats:italic>ONECUT2, SPEG, CTSE, GJB2<\/jats:italic>\n                      , and\n                      <jats:italic>SYNM<\/jats:italic>\n                      . Notably, 753 DEGs were unique to female patients, while 3989 were specific to males, with 1633 shared between both sexes. Functional annotation revealed that female-unique DEGs were significantly enriched in immune-related pathways, including regulation of leukocyte activation and cell\u2013cell adhesion, and lymphocyte differentiation. Whereas male-unique DEGs were predominantly associated with pathways related to cell cycle regulation, mitochondrial function, and androgen receptor signaling. Immune-related gene expression indicated that female-specific DEGs were involved in leukocyte activation and antigen receptor signaling, whereas male-specific DEGs were linked to B-cell activation and neutrophil-mediated immune responses. A two-factor interaction model identified\n                      <jats:italic>S100A14<\/jats:italic>\n                      as the only protein-coding gene whose expression exhibited a significant sex-dependent pattern, with four additional genes (\n                      <jats:italic>GJB2, DSC2, TM4SF<\/jats:italic>\n                      and\n                      <jats:italic>ALOX15B<\/jats:italic>\n                      ) showing a probable interaction effect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings provide preliminary evidence supporting further investigation of sex-specific approaches to BC management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12885-026-15666-3","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T12:05:29Z","timestamp":1770638729000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-related differences in gene expression in early-stage bladder cancer revealed by whole-transcriptome sequencing"],"prefix":"10.1186","volume":"26","author":[{"given":"Natalia","family":"Zeber-Lubecka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Bilski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michalina","family":"D\u0105browska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Goryca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Ziemska-Legi\u0119cka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Ostrowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Dobruch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa E.","family":"Hennig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"15666_CR1","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.eururo.2015.08.037","volume":"69","author":"J Dobruch","year":"2016","unstructured":"Dobruch J, Daneshmand S, Fisch M, Lotan Y, Noon AP, Resnick MJ, et al. 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