Galliera E, Marazzi M G, Vianello E, Drago L, Luzzati A, Bendinelli P, Maroni P, Tacchini L, Desiderio M A, Corsi Romanelli M M
Department of Biomedical, Surgical and Oral Science, Università degli Studi di Milano, Milan, Italy.
IRCCS Galeazzi Orthopedic Institute, Milan, Italy.
J Biol Regul Homeost Agents. 2016 Oct-Dec;30(4):1203-1208.
Despite the clinical importance of metastasis to the skeleton, the diagnostic tools for early detection and monitoring of bone metastasis lack sensitivity and specificity. We evaluated a promising new serum biomarker, the soluble form of the Receptor of Advanced Glycosylated End-products (sRAGE). sRAGE is involved in the Wnt-signaling pathway, and has been reported to reduce the risk of cancer. We investigated the diagnostic potential of sRAGE to improve the detection and monitoring of bone metastasis. We measured sRAGE in the serum of control healthy subjects, patients with primary tumors and patients with bone metastasis. sRAGE was also correlated with the Wnt inhibitors DKK-1 and sclerostin, the bone resorption markers MMP-2, MMP-9 and TRAP5, and the metastatic marker survivin. sRAGE was significantly lower in primary tumor and metastatic patients than in healthy subjects. sRAGE also showed a strong negative correlation with DKK-1, sclerostin, MMP-2, MMP-9, TRAP5b and survivin. These results indicated that sRAGE might play a protective role in bone metastasis progression, and it may diagnostic significance for detecting and monitoring osteolytic metastases.
尽管骨转移在临床上具有重要意义,但用于早期检测和监测骨转移的诊断工具缺乏敏感性和特异性。我们评估了一种有前景的新型血清生物标志物,即晚期糖基化终产物受体的可溶性形式(sRAGE)。sRAGE参与Wnt信号通路,并且据报道可降低癌症风险。我们研究了sRAGE在改善骨转移检测和监测方面的诊断潜力。我们检测了健康对照受试者、原发性肿瘤患者和骨转移患者血清中的sRAGE。sRAGE还与Wnt抑制剂DKK-1和硬化蛋白、骨吸收标志物MMP-2、MMP-9和TRAP5以及转移标志物生存素相关。原发性肿瘤患者和转移患者血清中的sRAGE显著低于健康受试者。sRAGE还与DKK-1、硬化蛋白、MMP-2、MMP-9、TRAP5b和生存素呈强负相关。这些结果表明,sRAGE可能在骨转移进展中发挥保护作用,并且它对溶骨性转移的检测和监测可能具有诊断意义。