Background and Objectives: Bone metastasis is the most frequent site of distant spread in breast cancer, yet reliable biomarkers capable of identifying patients at increased risk before metastatic disease becomes clinically evident remain limited. We investigated whether baseline serum Dickkopf-1 (DKK-1) and irisin levels were associated with subsequent bone and liver metastasis in patients with stage III breast cancer. Materials and Methods: Sixty-three patients with stage III breast cancer were retrospectively included. DKK-1 and irisin concentrations were measured using enzyme-linked immunosorbent assay in archived serum samples collected at the time of initial diagnosis, before the start of definitive treatment. Associations between biomarker levels and subsequent metastatic outcomes were evaluated using maximally selected rank statistics for cut-off determination, Kaplan–Meier survival analysis, restricted cubic spline analysis, and Cox proportional hazards regression models. Results: During follow-up, 29 patients developed bone metastasis. Baseline serum DKK-1 levels were significantly higher in patients who subsequently developed bone metastasis than in those who remained metastasis-free (p = 0.005), whereas irisin levels showed no significant difference. An exploratory optimal DKK-1 cut-off value of 66.75 pg/mL was identified. High baseline DKK-1 remained independently associated with bone metastasis-free survival after multivariable Cox proportional hazards regression including T stage, histological grade, Ki-67 index, lymphovascular invasion, irisin, ALP and CA15-3 (HR = 7.48, 95% CI 1.67–33.43, p = 0.008). Elevated baseline ALP was also independently associated with bone metastasis-free survival (BMFS) (HR = 4.12, 95% CI 1.35–12.53, p = 0.013). Neither DKK-1 nor irisin was significantly associated with subsequent liver metastasis. Conclusions: Elevated baseline serum DKK-1, but not irisin, was independently associated with shorter BMFS in patients with stage III breast cancer. Baseline DKK-1 may represent a candidate biomarker for identifying patients at increased risk of skeletal metastasis; however, these exploratory findings require external validation in prospective multicenter studies before any clinical implementation can be considered.

The study tests the efficacy of subconjunctival ranibizumab and bevacizumab treatments in determining the oxidant and antioxidant levels during alkali-induced corneal neovascularisation. The researchers assigned 24 New Zealand White rabbits into four different groups, which included a healthy control, an alkali-injured control, a BV-treated group, and an RN-treated group, with six rabbits per group. All animals received alkali injury treatment except for the HC group. The AC group received six doses of subconjunctival saline 24 h after their injury, while the BV group and RN group received one dose of 0.5 mg of their respective treatment. The researchers conducted 14-day assays on normal tissue, blood plasma, and erythrocytes to determine total antioxidant status and total oxidant status. The researchers performed biochemical assays for total antioxidant status TAS and total oxidant status TOS on samples that were collected after the 14-day observation period. The corneal TOS levels increased in all injured groups when matched against the HC group. The RN group showed the highest corneal TOS levels, but the difference between the RN and AC and BV groups did not reach statistical significance. The injured groups showed higher corneal TAS levels than HC (p = 0.002), but the AC, BV, and RN groups showed no differences. The injured groups showed a significant decrease in erythrocyte TAS compared with HC (p < 0.001), but the injured groups showed lower plasma TOS levels than HC (p < 0.001). The researchers found no other systemic differences between the groups that received anti-VEGF treatment. The study results show that alkali injury leads to both local and systemic changes in redox status. The two anti-VEGF agents caused numerical changes in corneal oxidative parameters, but these changes did not achieve statistical significance. The research requires further investigation to understand potential agent-related effects on corneal redox balance, which should take place in larger, more detailed studies.