Predictive significance of bone sialoprotein and osteopontin for bone metastases in resected Chinese non-small-cell lung cancer patients: A large cohort retrospective study

Abstract

Background Bone is one of the most common sites of metastasis in patients with non-small-cell lung cancer (NSCLC). Over-expression of bone sialoprotein (BSP) and osteopontin (OPN) in tumour samples has shown prognostic significance in bone metastasis (BM) of breast and prostate cancer, respectively. However, their importance in BM of NSCLC has not been verified. Therefore, we planned a large cohort retrospective study to investigate the relationship between the expression of these two biomarkers (BSP and OPN) and BM in surgically resected NSCLC patients. Methods 180 completely resected NSCLC patients were included in this study. 40 patients subsequently developed BM. Paraffin-embedded primary tumour tissues of patients were supplied to produce a tissue microarray, and immunohistochemistry method was used for evaluation of the expression of BSP and OPN. Different expressions of these two biomarkers among BM group and non-BM group were estimated by χ 2 test. BM-free survival was analyzed by Kaplan–Meier method. The prognostic impact of clinicopathologic variables and biomarker expression was evaluated by Cox proportional hazards model. Results BSP expression was associated with BM ( p = 0.007), whereas OPN expression did not reach statistical significance ( p = 0.245). Univariate analysis showed that expression of BSP ( p = 0.010) and N staging ( p < 0.005) was associated with BM-free survival. Multivariate analyses showed BSP expression (HR = 3.322, p = 0.003), N staging (HR = 1.879, p = 0.001), and T staging (HR = 1.618, p = 0.024) were independent prognostic factors for BM. Conclusions BSP protein expression in the primary resected NSCLC is strongly associated with BM and could be used to identify high-risk patients. Correlation of OPN protein expression and BM needs further investigation.