Wnt signaling pathway inhibitors as promising diagnostic serum markers of osteolytic bone metastasis

Abstract

Despite the clinical importance of bone metastases, we still know little about their onset and progression and current diagnostic tools lack the sensitivity and specificity required for clear early diagnosis. We therefore need to continue studying the pathogenesis of bone metastatic invasion in order to improve diagnosis. The Wnt pathway has been described as having an important role in bone carcinogenesis and metastatic progression. This study investigated the diagnostic potential of the two main Wnt inhibitors, sclerostin and DKK-1, to improve the detection of osteolytic bone metastases. We measured sclerostin and DKK-1, MMP-2 and MMP-9, the bone resorption marker TRAP5b and the metastatic marker survivin in a control group of healthy patients, in patients with primary tumors and in a group with metastasis. Sclerostin and DKK-1 were clearly high in primary tumor patients and even higher in metastatic patients, compared to controls. The close correlations with metastatic markers and bone resorption markers make sclerostin and DKK-1 promising as new biomarkers in the diagnosis of bone osteolytic metastases.