{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:31:04Z","timestamp":1786123864571,"version":"build-2736575974"},"reference-count":27,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"COMSATS University"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cancer Control"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">SOX2<\/jats:italic>\n                      , a key pluripotency gene, plays a central role in breast cancer stem cell (BCSC) biology, driving tumor aggressiveness. Although\n                      <jats:italic toggle=\"yes\">SOX2<\/jats:italic>\n                      dysregulation has been widely studied across various cancers, its specific regulatory mechanisms in breast cancer (BC) remain incompletely elucidated. This study examined the regulatory axis of the\n                      <jats:italic toggle=\"yes\">SOX2<\/jats:italic>\n                      gene and associated molecular mechanisms underlying BCSC maintenance and prognosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective cross-sectional study analyzed breast tumor tissues and adjacent normal controls collected consecutively from two tertiary hospitals.\n                      <jats:italic toggle=\"yes\">SOX2<\/jats:italic>\n                      promoter methylation was assessed using methylation-Specific PCR, and expression of\n                      <jats:italic toggle=\"yes\">SOX2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">DNMT3b, TET3<\/jats:italic>\n                      , miR-200b-3p, and\n                      <jats:italic toggle=\"yes\">TGF\u03b21<\/jats:italic>\n                      was quantified by qPCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Aberrant methylation of the\n                      <jats:italic toggle=\"yes\">SOX2<\/jats:italic>\n                      promoter, linked to increased expression, was observed in the BC cohort. Notably, several samples exhibited a poised promoter state, reflecting an epigenetic configuration associated with stemness. Upregulation of\n                      <jats:italic toggle=\"yes\">DNMT3b<\/jats:italic>\n                      in miR-200b-reduced cells was significantly associated with\n                      <jats:italic toggle=\"yes\">SOX2<\/jats:italic>\n                      promoter methylation, suggesting a feedback loop modulating methylation dynamics. Additionally, a positive association between deregulated\n                      <jats:italic toggle=\"yes\">TET3<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">TGF\u03b21<\/jats:italic>\n                      highlights a positive feedback loop in the dynamic tumor microenvironment.\n                      <jats:italic toggle=\"yes\">SOX2<\/jats:italic>\n                      methylation emerged as a strong prognostic marker, characterized by a low hazard ratio and high diagnostic sensitivity. Its combination with\n                      <jats:italic toggle=\"yes\">DNMT3b<\/jats:italic>\n                      improved specificity (SE = 90%, SP = 79%). Reduced\n                      <jats:italic toggle=\"yes\">TET3<\/jats:italic>\n                      and miR200b expression correlated with poor outcomes, and their integration with SOX2 formed a tri-gene signature that enhanced patient stratification. Correlation analyses revealed coordinated expression among\n                      <jats:italic toggle=\"yes\">SOX2, TET3<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">TGF\u03b21<\/jats:italic>\n                      , supporting their role in methylome regulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings underscore the clinical significance of this axis and its embedded feedback circuits in shaping BC progression and therapeutic response.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10732748261469370","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T18:44:14Z","timestamp":1785955454000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Significance of SOX2 Promoter Methylation in Breast Cancer Prognosis"],"prefix":"10.1177","volume":"33","author":[{"given":"Farhan","family":"Maqbool","sequence":"first","affiliation":[{"name":"COMSATS University Islamabad (CUI)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfar","family":"Ahamed","sequence":"additional","affiliation":[{"name":"COMSATS University Islamabad (CUI)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9371-7902","authenticated-orcid":false,"given":"Summaya","family":"Anwar","sequence":"additional","affiliation":[{"name":"COMSATS University Islamabad (CUI)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muqadas","family":"Fatima","sequence":"additional","affiliation":[{"name":"COMSATS University Islamabad (CUI)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"Zahra","sequence":"additional","affiliation":[{"name":"COMSATS University Islamabad 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