# Association Between CKAP4 Expression and Poor Prognosis in Patients with Bladder Cancer Treated with Radical Cystectomy

## TL;DR

This study shows that high CKAP4 levels in bladder cancer cells are linked to worse outcomes after surgery, suggesting it could help predict cancer recurrence.

## Contribution

The study identifies CKAP4 as a novel prognostic biomarker for bladder cancer recurrence after radical cystectomy.

## Key findings

- CKAP4-1 positivity was associated with shorter cancer-specific and recurrence-free survival.
- CKAP4-1 was an independent predictor of recurrence-free survival in multivariate analysis.

## Abstract

Cytoskeleton-associated protein 4 (CKAP4), which has been linked to worse outcomes in several types of cancer, has emerged as a novel biomarker to predict patient outcomes for bladder cancer following radical cystectomy. This study investigated CKAP4 levels in bladder cancer specimens after radical cystectomy, and the association between CKAP4 levels, clinicopathological characteristics, and patient outcomes was analyzed. The analysis revealed that CKAP4 was connected to a higher risk of cancer recurrence, which means that CKAP4 could be a useful clinical tool to predict cancer recurrence after surgery.

Background/Objectives: While cytoskeleton-associated protein 4 (CKAP4) has been associated with prognosis in various malignancies, its prognostic value for bladder cancer (BCa) remains unclear. The aim of this study was to evaluate CKAP4 expression in tumor cells and cancer-associated fibroblasts (CAFs) following radical cystectomy (RC) in patients with BCa. Methods: In this study, CKAP4 in tumor cells was defined as CKAP4-1, while CKAP4 expressed in CAFs was defined as CKAP4-2. CKAP4-2 expression was evaluated to explore its potential association with tumor aggressiveness and patient outcomes. CKAP4 expression in 86 RC specimens was assessed using immunohistochemistry. CKAP4-1 positivity was considered when ≥5% cytoplasmic staining of cancer cells, with at least moderate staining intensity, was observed. CKAP4-2 positivity was evaluated using a point scale (0–3), with scores based on the number of CKAP4 positive CAFs in the tumor stroma. Scores of 2 (moderate number of CAFs) and 3 (significant number of CAFs) were considered to indicate positivity. Results: CKAP4-1 and CKAP4-2 were expressed in 53 (61.6%) and 34 (39.5%) patients, respectively. Kaplan–Meier analysis showed that patients with CKAP4-1 had significantly shorter cancer-specific survival and recurrence-free survival (RFS; p = 0.046 and p = 0.0173, respectively). Multivariate analysis showed that CKAP4-1 positivity was an independent predictor of RFS (p = 0.041, hazard ratio: 2.09, 95% confidence interval: 1.03–4.25). Conclusions: This study showed that CKAP4 expression in tumor cells may serve as a useful prognostic biomarker for patients with BCa who undergo RC.