Abstract
Cisplatin-containing chemotherapy represents the first-line treatment for patients with locally advanced or metastatic muscle-invasive bladder cancer. Recently, novel therapies have become available for cisplatin-ineligible or -resistant patients. Therefore, prediction of cisplatin response is required to optimize therapy decisions. Syndecan-1 (SDC1) tissue expression and serum concentration may be associated with cisplatin resistance. Thus, pre-treatment serum levels of SDC1 and its expression in chemo-naïve tissues were assessed in 121 muscle-invasive bladder cancer patients who underwent postoperative platinum-based chemotherapy. SDC1 concentrations were evaluated by ELISA in 52 baseline and 90 follow-up serum samples and tissue expressions were analyzed by immunohistochemistry in an independent cohort of 69 formalin-fixed paraffin-embedded tumor samples. Pre-treatment SDC1 serum levels were significantly higher in lymph node metastatic (p = 0.009) and female patients (p = 0.026). SDC1 tissue expression did not correlate with clinicopathological parameters. High pre-treatment SDC1 serum level and the presence of distant metastasis were independent risk factors for overall survival (Hazard ratio (HR): 1.439, 95% Confidence interval (CI): 1.003–2.065, p = 0.048; HR: 2.269, 95%CI: 1.053–4.887, p = 0.036). Our results demonstrate an independent association between high baseline serum SDC1 concentration and poor survival in platinum-treated patients. Analyzing baseline serum SDC1 levels may help to predict platinum-containing chemotherapy and could help to optimize therapeutic decision-making.
Highlights
Urothelial bladder cancer (BC) is a common malignancy with approximately 550,000 new cases worldwide each year [1]
Our results demonstrate that high pre-treatment serum SDC1 levels are independently associated with poor survival in platinum-treated BC patients
In BC, we previously demonstrated that high preoperative serum levels of SDC1 are associated with progressed tumor stages, the presence of lymph node metastases, and are independently associated with poor patient survival [14]
Summary
Urothelial bladder cancer (BC) is a common malignancy with approximately 550,000 new cases worldwide each year [1]. In former studies, the relevance of other molecular alterations for platinum resistance was published, such as increased ERCC1 gene and protein expressions, and high survivin and HMGA2 tissue expressions were associated with poor response to platinum therapy of BC [10,11,12]. None of these molecular markers has been integrated into the clinical decision-making. We determined pre-treatment serum concentrations and tissue expressions of SDC1 in BC patients who received platinum-containing chemotherapy. We determined the serum MMP-7 level to examine the correlation with SDC1 concentration
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