Expression of melanoma-associated antigen-C2 in breast cancers and mechanism

Abstract

Objective: To analyze the expression pattern, mechanism and clinical significance of melanoma-associated antigen-C2 (MAGE-C2) in tumor-free breast specimens, breast benign disease specimens and breast cancer specimens. Methods: Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to investigate the expressions of MAGE-C2 in 60 tumor-free breast specimens, 60 breast benign disease specimens and 60 breast cancer specimens. The correlation of MAGE-C2 expression with clinicopathological parameters and prognosis of breast cancer patients were analyzed. The expression of MAGE-C2 was also detected by RT-PCR in breast cancer cell MCF-7 and MDA-MB-231 treated with DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) and histone deacetylase inhibitor trichostatin A (TSA). Results: The positive expression rates of MAGE-C2 mRNA and protein were 61.7% (37/60) and 58.3% (35/60) in breast cancer specimens, respectively, while negative expressed in breast and begin disease specimens. MAGE-C2 protein expression was associated with tumor grade, histological type and blood vessel invasion of breast cancer patients (P<0.05). The incidence of recurrence-free survival of patients with positive MAGE-C2 expression were lower than that of patients with negative MAGE-C2 expression (P<0.05). Multivariate Cox regression analysis showed that the clinical stage (P<0.01), lymph node metastasis (P<0.05) and MAGE-C2 expression (P<0.05) were the independent prognostic factors of breast cancer patients. The MAGE-C2 mRNA was not observed in the control and TSA treated breast cancer cells while upregulated in the 5-aza-CdR treated cells. Besides, 5-aza-CdR combined with TSA further enhanced MAGE-C2 mRNA level in breast cancer cells (P<0.05). Conclusions: MAGE-C2 is one of the tumor-specific antigen and its expression is related with the poor prognosis of breast cancer patients. DNA methylation and histone acetylation may be an important regulation mechanism of MAGE-C2 gene expression.