Study On The Relationship Of MAGE-A1 Expression And Tumor Cell Proliferation In Lung Carcinoma

ABSTRACT : BACKGROUND&OBJECTIVE: A possible close association between the expression of some members of tumor-specific antigen-MAGE(Melanoma antigen) family and infantile cells proliferated actively was revealed in some recent studies. But the correlation between MAGE-A1 expression proliferation of tumor cells and immune response at host local site has not been reported to date. And the study on the relationship of MAGE-A1 expression with cell proliferation and cell cycle distribution under the cultivation condition of tumor cell line in vitro has not been found. Our study is to investigate the expression of MAGE-A1 in non-small cell lung carcinoma(NSCLC), and the relationship between MAGE-A1 expression Ki-67 expression tumor-infiltrating lymphocytes(TIL) response histologic grade and pathological type. Meanwhile, to study the different expression of MAGE-A1 and its correlation with proliferation of tumor cells and cell cycle distribution in lung adenocarcinoma cell line A549 synchronized.METHODS: 30 NSCLC patients were examined for MAGE-A1, Ki-67 and TIL response by using SP immunohistochemical technique on formalin-fixed, paraffin-embedded sections. A549 cell line was cultivated and synchronized, the different expression level of MAGE-A1 and Ki-67 genes was quantitative detected in A549 cell line with or without synchronization by flow cytometry (FCM) and laser scanning confocal microscopy (LSCM) ,the cell cycle distribution was examined by FCM.RESULTS: MAGE-A1 was positive in 80.00%(24/30)in NSCLC, among these positive cases 46.67% (14/30) was high expression and 33.33% (10/30) was low expression.Ki-67 expression is 93.33%(28/30), among which 53.33%(16/30) was high expression and 40.00%(12/30) was low expression. TIL response was observed in 22 patients, there was a significant relationship between the positive expression of MAGE-A1 and Ki-67 positive expression ( rs =0.578, P<0.005),as well as between MAGE-A1 positive expression and TIL response ( rs =0.505 , P<0.005).However,MAGE-A1 expression was not significantly correlated to histologic grade and pathological type(P>0.05). The slightly detecting of MAGE-A1 expression in normal cultivated A549 group was showed in FCM result. Its expression level was increased after treatment of synchronization in S and Ga/M cell phase groups , the expression reached a high degree in G2/M group. MAGE-A1 positive signal in Gj group has not significant relationship with group of normal cultivation (P>0.05), in contrast to MAGE-A1 expression of S and G2/M cell groups compared to which in normal cultivation group (P0.05, P0.001 ). MAGE-A1 positive expression was correlated with cell cycle distribution (rs=0.583, P0.05). The similar result is given by LSCM . In addition, there was a significant positive correlation between MAGE-A1 and Ki-67 expression level in different treatment groups (rv =0.792, P0.005).CONCLUSION: MAGE-A1 expression in NSCLC was probably correlated with the increase of tumor cells' proliferation and TIL response, indicated that the value of MAGE-A1 expression as a potential target for immunotherapy in NSCLC patient whose tumor cells proliferate aggressively need further study. The change of MAGE-A1 expression intensity was accompanied with different cell cycle distribution , expression and regulation of MAGE-A1 gene was concerned with cell cycle, it need more research on the mechanism.