Increased hepcidin expression in non-small cell lung cancer tissue and serum is associated with clinical stage.

Abstract

Hepcidin is a small secreted peptide that plays a key role in iron metabolism. A high level of hepcidin expression may be implicated in colorectal cancer; however, the relationship between hepcidin and lung cancer has not yet been studied. Serum hepcidin-25, bone morphogenetic protein (BMP)-2, and interleukin (IL)-6 concentration in 53 patients and 16 non-cancerous individuals was measured by enzyme-linked immune sorbent assay. Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was utilized to study the expression of hepcidin mRNA in paired tumor and non-tumor lung tissues in surgical specimens from 65 patients with non small cell lung cancer (NSCLC), as well as in six types of lung cancer cell lines and human bronchial epithelial (HBE) cells. Hepcidin protein expression and cellular localization in NSCLC was determined by immunohistochemistry. The serum hepcidin-25 concentration was higher in patients with NSCLC than in non-cancerous individuals, and was positively correlated with serum BMP2 concentration, but negatively with serum IL-6 levels. Serum hepcidin was also correlated with lymph node metastasis and clinical stage. Hepcidin mRNA expression was higher in cancerous tissues of NSCLC than in normal pulmonary tissues (P = 0.001). Hepcidin mRNA levels in four lung carcinoma cell lines were higher than in HBE cells. Immunohistochemistry showed that hepcidin protein was increased in cancerous tissues of NSCLC. The level of hepcidin expression increased in NSCLC tissue and serum. Serum hepcidin-25 level was associated with lymph node metastasis and tumor clinical stage in patients with NSCLC.