Serum CEACAM1 Level Is Associated with Diagnosis and Prognosis in Patients with Osteosarcoma

Abstract

Carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1) is a trans-membrane multifunctional cell adhesion molecule associated with tumor cell proliferation, apoptosis, angiogenesis, invasion, and migration during tumor development. In the present study, we evaluated serum CEACAM1 level in osteosarcoma patients to explore its diagnostic and prognostic value for this particular malignancy. Sera from 113 patients with primary osteosarcoma, 98 patients with benign bone tumors and 126 healthy controls were obtained. Serum CEACAM1 level was measured with ELISA and correlation with clinicopathological characteristics was further analyzed. Receiver operating curves (ROC), Kaplan-Meier curves, and log-rank analyses as well as Cox proportional hazard models were used to evaluate diagnostic and prognostic significance. The results revealed that serum CEACAM1 level was significantly higher in osteosarcoma patients compared to benign bone tumors and healthy controls (455.2 ± 179.9 vs 287.4 ± 103.2, 260.8 ± 109.7 pg/ml, respectively). Osteosarcoma patients with larger tumors, later-tumor stages, low tumor grades, and distant metastases had much higher CEACAM1 compared to those with smaller tumors, earlier tumor stages, high tumor grades and non-distant metastases (P < 0.05 for all). Multivariate logistic regression analysis confirmed that high serum CEACAM1 level was an independent risk factor for distant metastases (OR = 3.02, 95%CI 1.65-4.17). To distinguish osteosarcoma patients from those with benign bone tumor and healthy controls, ROC/AUC analysis indicated an AUC of 0.81 (sensitivity 0.61; specificity 0.89) and an AUC of 0.77 (sensitivity 0.57; specificity 0.92), respectively. Osteosarcoma patients with higher CEACAM1 had relatively lower survival compared to those with low CEACAM1 (P < 0.01), and multivariate analyses for overall survival revealed that high serum CEACAM1 level was an independent prognostic factor for osteosarcoma (HR = 1.56, 95%CI 1.23-3.28). The present study suggested that elevated serum CEACAM1 level might be a novel diagnostic and prognostic biomarker for osteosarcoma patients.

Fig 1. Serum CEACAM1 concentration among OS patients, benign bone tumor and healthy controls.

Fig 2. Correlation analysis between serum CEACAM1 level and OS patients characteristics; Serum CEACAM1 level among OS patients with different tumor size (a); different clinical stages (b); different tumor grades (c); with and without distant metastases (d).

Fig 3. ROC analysis for serum CEACAM1 for distinguishing OS patients from benign bone tumors or healthy controls; ROC for serum CEACAM1 differentiating OS patients from controls (a); from those with benign bone tumors (b); distinguishing OS patients with IIB/III stages from those with IIA stages (c).

Fig 4. Kaplan-Meier survival curves; overall survival for OS patients with high serum CEACAM1 level compared to those with low CEACAM1 (P < 0.01).

Fig 5. CEACAM1 expression level in OS tumor tissue; CEACAM1 mRNA (a) and protein (b) expression of tumor tissues and tumor-adjacent tissues.