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.


BACKGROUND
ClinicalTrials.gov NCT02895178.
Department of Physiology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea.|Yonsei Institute of Sports Science & Exercise Medicine, Wonju, Republic of Korea.
Tae Ho
TH
Kim
Department of Physiology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea.|Yonsei Institute of Sports Science & Exercise Medicine, Wonju, Republic of Korea.
Jae Seung
http://orcid.org/0000-0002-4047-1128
JS
Chang
Department of Physiology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea.
Kyu-Sang
KS
Park
Department of Nursing Science, Kyungsung University, Busan, Republic of Korea.
Jeeyeon
J
Park
Department of Basic Nursing Science, Keimyung University College of Nursing, Daegu, Republic of Korea.
Nahyun
N
Kim
Department of Hematology-Oncology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea.
Jong In
JI
Lee
Department of Physiology, Wonju College of Medicine, Yonsei University, Wonju, Republic of Korea.|Yonsei Institute of Sports Science & Exercise Medicine, Wonju, Republic of Korea.
In Deok
ID
Kong
D000328:Adult; D015415:Biomarkers; D001823:Body Composition; D001943:Breast Neoplasms / Q000097:blood* / Q000453:epidemiology* / Q000628:therapy; D003131:Combined Modality Therapy; D004797:Enzyme-Linked Immunosorbent Assay; D015444:Exercise; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D009367:Neoplasm Staging; D012307:Risk Factors; D017741:Survivors; D000094742:Secreted Frizzled-Related Proteins
D015415:Biomarkers; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C501126:DKK1 protein, human; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins