Heterotopic production of ceruloplasmin by lung adenocarcinoma is significantly correlated with prognosis.

OBJECTIVES: Ceruloplasmin (CP) is a well-known copper binding protein synthesized mainly in the liver, but its expression is known to be elevated in the serum of cancer patients and in malignant tumor cells. Lung cancer is the leading cause of cancer-related death worldwide, and adenocarcinoma is the main histological type of lung cancer. However, the role of CP in lung adenocarcinoma is still unclear. Here we examined and compared the expression of CP in various histological subtypes of lung adenocarcinoma and its correlation with clinicopathological parameters.

MATERIALS AND METHODS: We examined CP expression in lung adenocarcinoma samples and cell lines using quantitative real-time RT-PCR and Western blot analysis. Immunohistochemistry for CP was carried out using 196 specimens of lung adenocarcinoma.

RESULTS: CP expression was significantly higher in invasive adenocarcinoma than in adenocarcinoma in situ (AIS), and was significantly correlated with poorer outcome, pathological stage, pT, and pN. Multivariate analysis showed that CP expression was an independent prognostic factor for lung adenocarcinoma patients. Furthermore, Western blot analysis using protein extracted from lung adenocarcinoma cell lines revealed the secreted form of CP.

CONCLUSION: CP is produced heterotopically in lung adenocarcinoma cells and its expression is associated with tumor progression. In view of the presence of the secreted form of CP in tumor cells, CP may be a useful biomarker for lung adenocarcinoma.