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.
晚期糖基化终末产物受体（RAGE）通过驱动肿瘤微环境中的慢性炎症，在前列腺癌的生长、侵袭和转移过程中发挥重要作用。本系统性综述与荟萃分析总结并分析了当前临床与临床前研究数据，旨在阐明RAGE表达水平与前列腺癌、肿瘤分级及分子效应之间的关联。通过多数据库检索，筛选出探讨前列腺癌中RAGE表达的原始临床与临床前研究文献。经筛选评估后，共纳入9篇临床研究与6篇临床前研究文献。采用比值比及其95%置信区间评估RAGE在区分良性前列腺增生或正常前列腺组织与前列腺癌、以及不同肿瘤分级间的表达差异。鉴于研究异质性，采用随机效应模型计算合并效应值。临床荟萃分析显示：与良性前列腺增生或正常前列腺组织相比，前列腺癌组织中RAGE表达显著升高（比值比：11.3；95%置信区间：4.4–29.1）；与低级别前列腺癌相比，高级别前列腺癌中RAGE呈现过表达（比值比：2.5；95%置信区间：1.8–3.4）。此外，通过信天翁图生成的临床前研究荟萃分析表明，RAGE表达/激活与前列腺癌生长及转移潜能呈显著正相关。本综述证实RAGE表达与前列腺癌进展密切相关，可作为区分健康前列腺、低级别前列腺癌和高级别前列腺癌的有效诊断靶标，并具有诊疗一体化的应用潜力。
RAGE as a Novel Biomarker for Prostate Cancer: A Systematic Review and Meta-Analysis
肿瘤(癌症)患者之家