Prognostic role of high cathepsin D expression in breast cancer: a systematic review and meta-analysis

Background: High cathepsin D has been associated with poor prognosis in breast cancer; however, the results of many studies are controversial. Here, we assessed the association between high cathepsin D levels and worse breast cancer prognosis by conducting a meta-analysis.

Methods: A comprehensive search strategy was used to search relevant literature in PUBMED and EMBASE by September 2018. The meta-analysis was performed in Review Manager 5.3 using hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: A total of 15,355 breast cancer patients from 26 eligible studies were included in this meta-analysis. Significant associations between elevated high cathepsin D and poor overall survival (OS) (HR = 1.61, 95% CI: 1.35-1.92, p < 0.0001) and disease-free survival (DFS) (HR = 1.52, 95% CI: 1.31-2.18, p < 0.001) were observed. In the subgroup analysis for DFS, high cathepsin D was significantly associated with poor prognosis in node-positive patients (HR = 1.38, 95% CI: 1.25-1.71, p < 0.00001), node-negative patients (HR = 1.78, 95% CI: 1.39-2.27, p < 0.0001), early stage patients (HR = 1.73, 95% CI: 1.34-2.23, p < 0.0001), and treated with chemotherapy patients (HR = 1.60, 95% CI: 1.21-2.12, p < 0.001). Interestingly, patients treated with tamoxifen had a low risk of relapse when their cathepsin D levels were high (HR = 0.71, 95% CI: 0.52-0.98, p = 0.04) and a high risk of relapse when their cathepsin D levels were low (HR = 1.50, 95% CI: 1.22-1.85, p = 0.0001).

Conclusions: Our meta-analysis suggests that high expression levels of cathepsin D are associated with a poor prognosis in breast cancer. Based on our subgroup analysis, we believe that cathepsin D can act as a marker for poor breast cancer prognosis and also as a therapeutic target for breast cancer.