Expression And Significance Of Melanoma Antigen-As In Tissues And Peripheral Blood Of Patients With Lung Cancer

Cancer is a serious public health problem in the world.Nowadays,the most common cause of cancer death is lung cancer,colorectal cancer,prostate cancer and breast cancer,these four kinds of cancer accounts for almost half of all cancer deaths.And lung cancer is the main cause of global cancer deaths.With the development of medical level,immunotherapy has become a new trend,which could be another treatment pattern following three major tumor therapies including surgery,chemotherapy and radiotherapy.It has the advantages of small trauma and strong targeting.However,to identify effective target antigens is the critical in immunotherapy.Cancer / testis antigens(CTA)have a specific expression pattern,so it can be used as a specific target for tumor immunotherapy.In recent years,our group has focused on the expression,biological function and clinical significance of the MAGE-A in different tumors.In this present study,immunohistochemical staining and fluorescence in situ hybridization were used to detect the expression of MAGE-A(including MAGE-A1,-A2,-A3,-A4,-A6,-A10 and-A12)in NSCLC and its adjacent tissues,EGFR amplification and ALK rearrangement,and the relationship with clinical biology.The relationship between the expression of MAGE-As gene and the clinical prognosis in patients with lung cancer.The main contents and results are as follows: Part I Expressions of melanoma antigen-As by immuno-histochemical staining to tissue microarrayin non-small cell carcinomaObjective: To investigate the expression of melanoma antigen(MAGE)-As in non-small cell carcinoma(NSCLC),explore their correlation with clinical biological indicators and the prognostic factors.Methods:1 We purchased 90 cases of non-small cell lung cancer and its adjacent tissue microarray.Immunohistochemical staining was used to detect the protein expression of MAGE-As protein in carcinoma and adjacent NSCLC tissue and the clinical indicators were analyzed.2 EGFR gene amplification and ALK gene rearrangements of NSCLC patients were detected by fluorescent in situ hybridization(FISH),the association between MAGE-A expression and the EGFR gene amplification and ALK gene rearrangements was also analyzed.Results:1 The positive rates of MAGE-As protein in NSCLC tumor tissue were 45.56%(41/90).2 MAGE-As protein expression was not correlated with clinical biological indicators in patients with NSCLC,EGFR gene amplification and ALK gene rearrangements(P>0.05).3 Log-rank test showed that the survival time of MAGE-As protein expression were lower than those negative ones in patients with NSCLC(P=0.002).EGFR gene amplification and ALK gene rearrangements were not associated with the overall survival of NSCLC patients.4 Results from multivariate analyses showed that the expression of MAGE-As protein,clinical stage,lymph node metastasis were independent risk factors of NSCLC.Conclusions: MAGE-As proteins may be NSCLC-associated antigens,thus having potential diagnostic and prognostic significance in clinical settings.Part ? Expression and clinical significance of MAGE-As mRNA in peripheral blood of lung cancer patientsObjective: To detect the expression of MAGE-As gene in peripheral blood of lung cancer patients,the clinical indicators were analyzed.Methods:1 Multiplex nested RT-PCR was used to detect the level of MAGE-As mRNA in peripheral blood circulating tumor cells of 122 cases lung cancer patients and 30 cases health donors.2 Restriction endonuclease treatment was used to detect the expression of each member of MAGE-As family,including MAGE-A1,-A2,-A3,-A4 and-A6 mRNA.Results:1 Expression rate of MAGE-A mRNA was 17.21%(21/122)in lung cancer patient peripheral blood,which was detected by multi RT-nested PCR.The frequency of MAGE-As mRNA expression in lung cancer patient peripheral blood was the following order: A2>A6>A4>A3>A1.Expression rate of MAGE-A1 mRNA was 2.46%(3/122),MAGE-A2 15.57%(19/122),MAGE-A3 9.02%(11/122),MAGE-A4 12.30%(15/122),MAGE-A6 13.93%(17/122).2 Expression of MAGE-As mRNA in lung cancer patient peripheral blood was statistically significant with patient clinical stage,tumor size,lymphatic metastasis,distal metastasis,radiotherapy and/or chemotherapy and ages(all P<0.05).MAGE-As mRNA expression of lung cancer patient peripheral blood was not significance associated with gender,pathological pattern,smoking history,drinking history(all P<0.05).3 MAGE-A2,MAGE-A3,MAGE-A4 and MAGE-A6 mRNA expressions in lung cancer patient peripheral blood were positively correlated with patient clinical stage,tumor size,lymph node metastasis and distal metastasis of patients with lung cancer(all P<0.05).Otherwise,The MAGE-A1 mRNA expression rate of lung cancer patients with distal metastasis was significantly higher than patients without distal metastasis(P<0.01).MAGE-A2,MAGE-A3,and MAGE-A6 mRNA expressions rate of lung cancer patients with radiotherapy and/or chemotherapy was significantly lower than patients without radiotherapy and/or chemotherapy(all P<0.05).Conclusion: MAGE-As mRNA expression in peripheral blood of lung cancer may be as a important maker for lung cancer.Expression of MAGE-As mRNA may be correlated with prognosis of lung cancer,so as to do an important marker for monitoring the treatment and prognosis of lung cancer.