{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T10:04:35Z","timestamp":1771581875595,"version":"3.50.1"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Bladder cancer management is challenged by limited therapeutic targets and heterogeneous treatment responses. Ribosomal S6 kinase 4 (RSK4) has been established as an oncogenic driver in several malignancies, although its clinical significance in bladder cancer remains undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate RSK4 protein expression in bladder cancer specimens and assess its association with clinicopathologic features and patient outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>RSK4 expression was analyzed by immunohistochemistry in a retrospective cohort of 143 bladder cancer specimens, including 93 cases represented in a tissue microarray. Statistical analyses were performed to evaluate the associations between RSK4 expression levels, standard clinicopathological parameters, and overall survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>RSK4 immunoreactivity was detected in 65.7% (94\/143) of tumor tissue samples but in 36.5% (23\/63) of matched normal urothelial tissue samples (P &amp;lt; 0.0001). Elevated RSK4 expression was significantly correlated with the following established markers of disease progression: muscularis propria invasion (P &amp;lt; 0.001), high tumor grade (P &amp;lt; 0.01), advanced TNM stage (P &amp;lt; 0.001), lymph node metastasis (P &amp;lt; 0.01), and distant metastasis (P &amp;lt; 0.05). No significant associations were observed with patient age, sex, or tumor size. Multivariate analysis confirmed RSK4 as an independent predictor of reduced overall survival (HR = 2.34, 95% CI 1.42\u20133.85, P &amp;lt; 0.001). Subcellular studies indicate that RSK4 overexpression enhances the invasive and metastatic capabilities of bladder cancer cell lines, and vice versa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study elucidates the expression pattern and mechanism of action of RSK4 in bladder urothelial carcinoma, confirming that its overexpression is a key factor for predicting poor prognosis. This discovery highlights the potential value of RSK4 as a significant therapeutic target, providing a new theoretical basis for improving clinical outcomes in bladder cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1757293","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T09:06:03Z","timestamp":1771578363000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Expression of ribosomal S6 kinase 4 in bladder cancer and its correlation with clinicopathological features"],"prefix":"10.3389","volume":"16","author":[{"given":"Zhenzhen","family":"Li","sequence":"first","affiliation":[{"name":"Yan\u2019an Medical College, Yan\u2019an University","place":["Yan\u2019an, China"]},{"name":"State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Pathology, School of Basic Medicine and Xijing Hospital, Fourth Military 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