Evaluation of CXCL12, carbohydrate antigen CA15.3, calcium and parathyroid hormone as potential biomarkers for bone metastasis in patients with breast cancer

Bone is a common site for tumor cells to settle in breast cancer. It has been reported that ~70% of patients with breast cancer experience bone metastasis. C‑X‑C motif chemokine ligand 12 (CXCL12) is a chemokine, which plays a crucial role in bone metastasis. Currently, the diagnostic biomarkers and risk factors associated with bone metastasis are limited. Therefore, the present study aimed to investigate whether CXCL12, carbohydrate antigen 15.3 (CA15.3), a comparative biomarker, and the bone‑related biomarkers, calcium (Ca²⁺) and parathyroid hormone (PTH), could be used as diagnostic biomarkers and independent risk factors for the early detection and treatment of bone metastasis in patients with breast cancer. The present case control and cross‑sectional study consisted of 25 participants who served as the control group, 25 patients newly diagnosed with breast cancer, 25 patients treated for primary breast cancer and 20 patients with breast cancer and bone metastasis. The CXCL12, CA15.3 and PTH levels were analyzed using sandwich ELISA. In addition, the Ca²⁺ levels were measured using colorimetric assay. The results revealed that the levels of CXCL12 were significantly increased. In addition, the levels of Ca²⁺ were slightly increased, whereas the PTH levels were notably decreased in patients with breast cancer experiencing bone metastasis. In addition, CXCL12 exhibited a higher diagnostic accuracy [area under the curve (AUC), 0.7940; P=0.0008] at a cut‑off value of >1,392 pg/ml compared with CA15.3 (AUC, 0.6579; P=0.0756; cut‑off, >21.50 U/ml). Additionally, PTH displayed a higher diagnostic accuracy (AUC, 0.7280; P=0.0092) for bone metastasis compared with Ca2+ (AUC, 0.6792; P=0.0427). Notably, the diagnostic accuracy was increased (AUC, 0.8040; P=0.0005) after combining CXCL12 and CA13.5. Furthermore, CXCL12, CA15.3 and PTH were identified as independent risk factors for bone metastasis. Overall, the results of the present study suggest that CXCL12, CA15.3 and PTH may be considered as promising independent risk factors, which could assist the early detection of bone metastasis and the selection of treatment for patients with breast cancer.