RAGE as a Novel Biomarker for Prostate Cancer: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: Prostate cancer (PCa) is a commonly diagnosed cancer among men worldwide, and the current research aims to understand the molecular factors that may help to diagnose or treat PCa. This study was conducted to evaluate all existing literature measuring the expression of the receptor for advanced glycation end-products (RAGE) in PCa using both clinical biopsies and preclinical research, performed using cell culture. Importantly, the results of this study can be used to diagnose PCa, as the results demonstrate that RAGE is more highly expressed in malignant compared to benign tissues. Additionally, the results show that RAGE activity in PCa cells activates growth, suggesting that RAGE can also be used as a therapeutic target for treating PCa. One method to reduce RAGE expression and activity that is immediately actionable is to reduce the intake of dietary advanced glycation end-products (AGEs), which are found in high levels in the Western diet. ABSTRACT: The receptor for advanced glycation end-products (RAGE) has been implicated in driving prostate cancer (PCa) growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. This systematic review and meta-analysis summarizes and analyzes the current clinical and preclinical data to provide insight into the relationships among RAGE levels and PCa, cancer grade, and molecular effects. A multi-database search was used to identify original clinical and preclinical research articles examining RAGE expression in PCa. After screening and review, nine clinical and six preclinical articles were included. The associations of RAGE differentiating benign prostate hyperplasia (BPH) or normal prostate from PCa and between tumor grades were estimated using odds ratios (ORs) and associated 95% confidence intervals (CI). Pooled estimates were calculated using random-effect models due to study heterogeneity. The clinical meta-analysis found that RAGE expression was highly likely to be increased in PCa when compared to BPH or normal prostate (OR: 11.3; 95% CI: 4.4–29.1) and that RAGE was overexpressed in high-grade PCa when compared to low-grade PCa (OR: 2.5; 95% CI: 1.8–3.4). In addition, meta-analysis estimates of preclinical studies performed by albatross plot generation found robustly positive associations among RAGE expression/activation and PCa growth and metastatic potential. This review demonstrates that RAGE expression is strongly tied to PCa progression and can serve as an effective diagnostic target to differentiate between healthy prostate, low-grade PCa, and high-grade PCa, with potential theragnostic applications.