Introduction

Prostate cancer is the most diagnosed cancer among men worldwide. Current research evaluates the molecular factors that may guide in the diagnosis and treatment of PCa. This study analyzed all the literature measuring expression of the receptor for advanced glycation end-products (RAGE) in PCa using both clinical biopsies and preclinical research. RAGE has been implicated in driving PCa growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. 

Aim

This systematic review and meta-analysis investigate the association between RAGE expression in low-grade and high-grade PCa compared to normal prostate and benign prostatic hyperplasia (BPH), as well as the relationships between RAGE levels and PCa growth and markers of invasiveness and metastasis.

Method

• An extensive multi-database search was conducted to identify original clinical and preclinical research articles examining RAGE expression in PCa
• After screening and review, 9 clinical and 6 preclinical articles were included
• The associations of RAGE differentiating 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

Results

• All 9 clinical studies were retrospective case-control studies examining the incidence of RAGE expression in PCa samples vs benign controls
• The clinical meta-analysis indicated an extremely strong likelihood for PCa to express RAGE as compared to BPH or normal prostate (OR: 11.3)
• Greater RAGE expression was likely to be observes as PCa progresses highlighting that RAGE was overexpressed in high-grade PCa when compared to low-grade PCa (OR: 2.5)
• Meta-analysis of preclinical studies revealed that increased RAGE expression resulted in increased PCa cell proliferation
• Positive associations were noted among RAGE expression/activation and PCa growth and metastatic potential

Conclusion

• Receptor for advanced glycation end-products (RAGE) is more highly expressed in malignant tissues as compared to benign tissues.
• RAGE expression is strongly associated with prostate cancer (PCa) progression and can be used as an effective therapeutic target for treating PCa.
• These results provide immediately actionable evidence for clinical recommendations for dietary modification in PCa.

Cancers (Basel). 2023 Oct 9;15(19):4889. Doi: 10.3390/cancers15194889.