ORIGINAL RESEARCH article
Front. Oncol.
Sec. Genitourinary Oncology
Expression of Ribosomal S6 Kinase 4 (RSK4) in Bladder Cancer and its Correlation with Clinicopathological Features
Provisionally accepted
Zhenzhen Li1,2
Gongchen Wang1,2Siyu Tan1Yingmei Wang1Junyi Feng3CHen Wei1Jia Chai1,2
Yanru Yang1,2Xiaoyan Zhou3Jing Ma1,2*
Zhiyong Yin4*
Linni Fan1,2*- 1Department of Pathology, the First Affiliated Hospital of Air Force Medical University, Xi’an, China
- 2School of Basic Medicine, Air Force Medical University, Xi’an, China
- 3Yan’an Medical College, Yan’an University, Yan’an, China
- 4Department of Cardiology，The First Affiliated Hospital of Air Force Medical University, Xi’an, China
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Context.— 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. Objective.—To evaluate RSK4 protein expression in bladder cancer specimens and assess its association with clinicopathologic features and patient outcomes. Design.— 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. Results.— 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 < 0.0001). Elevated RSK4 expression was significantly correlated with the following established markers of disease progression: muscularis propria invasion (P < 0.001), high tumor grade (P < 0.01), advanced TNM stage (P < 0.001), lymph node metastasis (P < 0.01), and distant metastasis (P < 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 1.42–3.85, P < 0.001). Subcellular studies indicate that RSK4 overexpression enhances the invasive and metastatic capabilities of bladder cancer cell lines, and vice versa Conclusions.— 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.
Keywords: Bladder cancer, Immunohistochemistry, prognosis, RSK4, tissue microarray
Received: 30 Nov 2025; Accepted: 16 Jan 2026.
Copyright: © 2026 Li, Wang, Tan, Wang, Feng, Wei, Chai, Yang, Zhou, Ma, Yin and Fan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jing Ma
Zhiyong Yin
Linni Fan
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