Frontiers in oncology · 2026
Expression of ribosomal S6 kinase 4 in bladder cancer and its correlation with clinicopathological features.
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Li Zhenzhen, Wang Gongchen, Tan Siyu, Wang Yingmei, Feng Junyi, Wei CHen, Chai Jia, Yang Yanru, Yin Zhiyong, Zhou Xiaoyan, Ma Jing, Fan Linni
Аннотация
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.
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.