Effects of exercise training on circulating levels of Dickkpof-1 and secreted frizzled-related protein-1 in breast cancer survivors: A pilot single-blind randomized controlled trial

BACKGROUND: Wingless and integration site growth factor (Wnt) signaling is a tumorigenesis-related signaling pathway. Dickkpof-1 (DKK1) and secreted frizzled-related protein-1 (SFRP1) are endogenous negative regulators of Wnt/β-catenin signaling. Accumulating evidence indicates that higher serum levels of DKK1 are correlated with poor prognosis of various types of cancer. Here, we investigated whether exercise training causes changes in the serum levels of DKK1 and SFRP1 in patients with breast cancer. METHODS: Twenty-four breast cancer survivors, after chemo- or radiotherapy, participated in this single-blind randomized, controlled pilot study. Subjects were randomized to either an exercise program or a control group for 12 weeks and completed pre- and post-training tests for health-related fitness and body composition as well as blood biomarkers. The serum levels of DKK1 and SFRP1 were measured using enzyme-linked immunosorbent assay as the primary outcome. RESULTS: Exercise training for 12 weeks remarkably increased muscle strength, endurance, and flexibility and decreased body fat percentage, waist circumference, and visceral fat area (all p < 0.05). Exercise training lowered serum insulin levels and leptin/adiponectin ratios (all p < 0.05). The levels of DKK1 and SFRP1 were also significantly decreased by exercise training in breast cancer survivors (all p < 0.01). CONCLUSIONS: Our results indicate that DKK1 and SFRP1 may be potentially useful biomarkers for evaluating the beneficial effects of long-term exercise on physical fitness and metabolism as well as the prognosis of patients with cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT02895178