{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:09:10Z","timestamp":1788775750398,"version":"build-2803163510"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009162","name":"Universidade Estadual De Londrina","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009162","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Biol Rep"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Urothelial bladder carcinoma (UBC) is the ninth most common malignancy worldwide and ranks thirteenth in cancer-related mortality. A significant challenge in managing non-muscle-invasive UBC (NMIBC) is the high recurrence rate, compounded by a paucity of robust prognostic biomarkers. Given that evasion of apoptosis is a hallmark of carcinogenesis, the\n                      <jats:italic>apoptosis regulator BCL-2<\/jats:italic>\n                      oncogene plays a critical role by negatively regulating the intrinsic apoptotic pathway, often leading to protein overexpression and malignant cell immortalization. Methods and Results: This study evaluated the\n                      <jats:italic>BCL-2<\/jats:italic>\n                      allelic variants rs2279115 (G\u2009&gt;\u2009T) and rs3943258 (T\u2009&gt;\u2009C), including their haplotype structures, in association with BCL-2 immunohistochemical expression in UBC patients. Genetic and immunostaining data were analyzed alongside prognostic factors, environmental exposure, and clinical history. Furthermore, we sought to exhibit BCL-2 immunohistochemical staining patterns via immunofluorescence in selected samples. Our findings revealed that the rs2279115 variant is significantly associated with BCL-2 positive expression. Specifically, the TT genotype in the genotypic model (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.035) and the GT genotype in the overdominant model (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.045) were linked to protein status. Additionally, the CT haplotype was independently associated with high-grade tumors. Conclusions: The presence of the CT haplotype \u2014 in either homozygosity or heterozygosity \u2014 exerted a risk effect of high-grade (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.020). In conclusion, these findings suggest that\n                      <jats:italic>BCL-2<\/jats:italic>\n                      variants, haplotype structures, and immunohistochemical expression may offer relevant insights into the molecular characteristics of urothelial bladder cancer. Further prospective validation is needed to determine whether BCL-2 profiling can serve as a useful complementary tool for risk assessment in clinical practice.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11033-026-12697-8","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T09:25:13Z","timestamp":1788773113000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of BCL-2 rs2279115 and rs3943258 variants on protein expression and clinical outcome of urothelial bladder carcinoma"],"prefix":"10.1007","volume":"53","author":[{"given":"Julia Ayumi Ikeda","family":"Kawasaki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane Pereira","family":"de Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Pedro Rocha","family":"Pontes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana Mara","family":"Serpeloni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janaina Nicolau","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Lu\u00eds Laforga","family":"Vanzela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Terziotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilner","family":"Martinez-Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen Braj\u00e3o","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6291-8621","authenticated-orcid":false,"given":"Roberta Losi","family":"Guembarovski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"12697_CR1","unstructured":"Ferlay J Global Cancer Observatory: Cancer Today. 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