Yang Li, Bingxiang Wu, Wenjun Zhou
This study aimed to evaluate the clinical predictive value of combining N-terminal serum osteocalcin (N-MID) with thyroid transcription factor-1 (TTF-1) for bone metastasis in lung cancer. This retrospective analysis included 147 lung cancer patients admitted to the hospital between February 2020 and October 2024. Patients were divided into a bone metastasis group (n=83) and a non-bone metastasis group (n=64) based on the presence of bone metastases. Baseline clinical data and laboratory parameters, including TTF-1, N-MID, tumor abnormal protein (TAP), parathyroid hormone (PTH), vascular endothelial growth factor (VEGF), total N-terminal propeptide of type I collagen (tPINP), and β-C-terminal telopeptide of type I collagen (β-CTX) were collected. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for bone metastasis. Model performance was evaluated using receiver operating characteristic (ROC) curves, integrated discrimination improvement (IDI), category-based net reclassification improvement (cNRI), the Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis (DCA). Age-stratified analysis and external validation were further conducted to ensure the generalizability of study. Univariate analysis showed that TTF-1 positivity rate and the levels of TAP, PTH, VEGF, tPINP, β-CTX, and N-MID were significantly higher in the bone metastasis group than in the non-bone metastasis group (all P<0.05). Multivariate logistic regression confirmed that TTF-1 (OR=2.217, 95% CI: 1.329-3.698, P<0.001) and N-MID (OR=2.519, 95% CI: 1.404-4.518, P<0.001) were independent risk factors for bone metastasis in lung cancer. After adding TTF-1 and N-MID to a baseline model that included PTH, VEGF, tPINP, and β-CTX, the area under the curve (AUC) increased from 0.752 to 0.837, with an IDI of 0.079 and a cNRI of 0.609 (both P<0.001). The Hosmer-Lemeshow test indicated good model fit, and external validation demonstrated good concordance between predicted probabilities and observed outcomes. Age-stratified analysis revealed that in elderly populations (70-79 years and 80-89 years), the combined detection of TTF-1 and N-MID yielded significantly higher AUC than either marker alone. Decision curve analysis confirmed that the combined detection provided a higher net benefit within clinically reasonable threshold ranges. In conclusion, TTF-1 and N-MID are independent risk factors for bone metastasis in lung cancer, and their combination significantly enhances the diagnostic performance of the predictive model, with particularly notable clinical value in elderly patients. These findings provide evidence-based references for early identification of bone metastasis and individualized clinical intervention in lung cancer.