Abstract: Objective To evaluate the clinical value of transforming growth factor-β1 (TGF-β1), calcium ion (Ca²⁺) and bone-specific alkaline phosphatase (BALP) in patients with bone metastasis from hepatocellular carcinoma (HCC). Methods A total of 350 HCC patients were selected and divided into no bone metastasis group (n=304) and the bone metastasis group (n=46) according to clinical symptoms and imaging results. HCC patients with bone metastases were divided into single bone metastasis group (n=21) and multiple bone metastases group (n=25) according to PET-CT results. According to the occurrence of complications such as pathological fracture and spinal cord compression, the patients were divided into the non-complication group (n=40) and the complication group (n=6). The clinical data and serum TGF-β1, Ca²⁺and BALP levels of all groups were compared. TGF-β1, Ca²⁺and BALP levels were correlated with visual analog scale (VAS), modified Barthel Index Scale (BI) and bone metastases-specific sub-scale (QLQ-BM22) by Pearson correlation analysis. The receiver operating characteristic (ROC) curve was plotted to assess the efficacy of combining TGF - β 1, Ca²⁺, and BALP indicators in evaluating HCC with bone metastasis. Methods Bone metastasis occurred in 46 of 350 HCC patients (13.14%). The levels of ALP, AFP-L3, CEA, TGF-β1, Ca²⁺and BALP in bone metastasis group were 157.35±13.67 U/L, 138.47±12.18 μg/L, 11.69±2.53 μg/L, 58.95±7.26 μg/L, 2.74±0.39 μmol/L, 12 6.49±14.35 U/L, which were higher than that in the group without bone metastasis (97.35±8.73 U/L, 82.39±7.75 μg/L, 2.47±0.56 μg/L, 26.75±4.38 μg/L, 1.96±0.28 μmol/L, 51.74±6.18 U/L). The difference was statistically significant (F=9.581, 9.263, 13.582, 9.265, 6.527, 12.672, all P<0.05). In patients with bone metastasis, TGF-β1, Ca²⁺and BALP levels in patients with multiple bone metastasis were 73.16±8.41 μg/L, 2.95±0.48 μmol/L, 137.26±15.71 U/L. It was higher than that of patients with single bone metastasis (37.28±4.59 μg/L, 2.14±0.31 μmol/L, 69.45±8.02 U/L), and the difference was statistically significant (F=9.672, 8.427, 12.036, all P<0.05). The levels of TGF-β1, Ca²⁺and BALP were 79.56±9.25 μg/L, 3.02±0.51 μmol/L and 143.19±16.58 U/L in patients with bone metastasis complications. It was higher than that of patients without complications (35.47±4.38 μg/L, 2.17±0.32 μmol/L, 72.38±8.14 U/L), and the difference was statistically significant (F=10.247, 9.138, 13.257, all P<0.05). Pearson analysis showed that serum levels of TGF-β1, Ca²⁺and BALP in HCC patients with bone metastasis were positively correlated with VAS and QLQ-BM22 scores, and negatively correlated with BI scores (P<0.01). ROC curve showed that the area under the curve (AUC), sensitivity and specificity of the combined detection of TGF - β 1, Ca²⁺, and BALP were higher than that of any single item (P<0.01). Conclusion TGF-β1, Ca²⁺, and BALP have higher value in early warning and disease assessment of HCC patients with bone metastasis, and the combined detection has better efficacy.

Key words: HCC, Bone metastases, TGF-β1, Ca²⁺, BALP