Expression of ribosomal S6 kinase 4 in bladder cancer and its correlation with clinicopathological features

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.

To evaluate RSK4 protein expression in bladder cancer specimens and assess its association with clinicopathologic features and patient outcomes.

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.

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.

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.