{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T16:06:44Z","timestamp":1776874004175,"version":"3.51.2"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":111,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100006765","name":"Chinese Medical Association","doi-asserted-by":"publisher","award":["Z-2021\u201346-2101\u20132023"],"award-info":[{"award-number":["Z-2021\u201346-2101\u20132023"]}],"id":[{"id":"10.13039\/501100006765","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Breast Journal"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Integrin beta 4 (ITGB4) has been implicated in breast cancer progression, yet its clinical utility as a biomarker remains unclear due to inconsistent findings across studies. This discrepancy may stem from the failure to distinguish between RNA and protein levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed an integrated multiomics analysis of ITGB4 across breast cancer subtypes using data from TCGA, CPTAC, METABRIC, and GEO cohorts. Key findings were functionally validated using CDK4\/6 inhibition in luminal cells and via immunohistochemistry on triple\u2010negative breast cancer (TNBC) tissue microarrays.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ITGB4 exhibited significant RNA\u2013protein discordance across breast cancer subtypes. High ITGB4 protein expression predicted a favorable prognosis in ER\u2010positive breast cancer (HR\u2009=\u20090.58, 95% CI: 0.39\u20130.86,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007) and enhanced sensitivity to CDK4\/6 inhibitors. Conversely, high ITGB4 expression in TNBC correlated with immunotherapy resistance, characterized by elevated PD\u2010L1\/PD\u2010L2 expression and reduced cytotoxic lymphocyte infiltration. Mechanistically, we identified the ESR1\/miR\u2010342\u20105p\/UBE2E3 axis as a potential regulator of ITGB4 protein stability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ITGB4 protein expression serves as a bimodal biomarker in breast cancer, predicting CDK4\/6 inhibitor sensitivity in luminal subtypes while indicating immunotherapy resistance in TNBC. ITGB4 protein thus represents a critical biomarker for guiding personalized therapy in precision oncology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/tbj\/7668096","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T15:30:32Z","timestamp":1776871832000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrin Beta 4 Protein Expression Bimodally Predicts Sensitivity to CDK4\/6 Inhibition and Resistance to Immunotherapy in Breast 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