Expression And Its Clinical Significance Of Tumor-associated Antigen MAGE-A3/C2 In Non-small Cell Lung Carcinoma (NSCLC)

Background and objectivesAlong with the rising incidence in recent years,lung cancer has been the leading cause of death due to malignancies in our country and worldwide.The main therapeutic method of NSCLC are surgical resection for the early stage patients.Most patients without nonspecific symptoms at early stage had mostly lost the opporunity of surgical therapy when lung cancer was detected at advanced stage.For many decades,cytotoxic chemotherapy/radiotherapy was the only effective treatment to prolong survival in these patients,despite its many drawbacks and limited role.Therefore,searching for new effective treatments become an urgent need for clinical cancer therapy.Studies have shown that the development of tumor is closely related to the human immune system.The aim of immunotherapy is to specifcally enhance the immune response directed to the tumor.In recent years,several approaches to immunotherapy for lung cancer have shown promise in early clinical trials and in late-phase development.At this time of great expectations,this review provides the reader with an update on the immunotherapies used to treat lung cancer and an overview of the main perspectives within this field.The key for the success of cancer immunotherapy is to select an ideal target.Cancer-testis antigen(CTA)are widely studied in the field of cancer immunotherapy due to their restrictive expression in certain normal tissues(testis and placenta tissue)and various malignancies,but not in any other normal tissues.Melanoma-associated antigens(MAGE)are a group of well-characterized members of the cancer-testis antigen(CTA)family.MAGE expression was correlated with tumor growth,survival and disease recurrence in patients with malignant diseases.Downregulating the expression of MAGE in vitro could change the biological characteristics of tumor cells,including reducing the adhesion,invasion and metastasis ability.The expression of MAGE genes might be related to the poor prognosis of cancer,so it could be served as poor prognostic indicator for malignances.Immunotherapy targeting the family members such as MAGE-A3 might represent a potential therapeutic strategy for NSCLC,and MAGE-A3 antigen specific T-cell receptor(TCR)modified T cell therapy has recently shown to effectively kill lung cancer cells.Tumor tissues were collected from 206 NSCLC patients.Quantitative real time polymerase chain reaction(qRT-PCR)was performed to detect the mRNA expression levels of MAGE-A3 and MAGE-C2 for all samples.The correlation of clinicopathological characteristics(gender,age,histologic grading,pathological type,lymph node metastasis,stage)with the expressions of MAGE-A3/C2 mRNAs in tissue of patients with NSCLC was evaluated.Then we used small interfering RNA(siRNA)to evaluate the potential function of MAGE-A3 expression in NSCLC cells and biology in vitro.Methods1?From October 2014 to May 2016,206 non-small cell lung cancer(NSCLC)patients from the Biotherapy Center were enrolled in this randomized study.The patients who entered into this study were diagnosed pathologically as NSCLC.The selection criteria for operable patients included undergoing radical surgery for lung carcinoma,having the opportunity to get the tumor tissue.Written informed consent was obtained from all patients and there was no chemotherapy,radiotherapy or other therapy before entry into the study.This study was approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University.QRT-PCR(Quantitative real time polymerase chain reaction)was used to detect the mRNA expression level of MAGE-A3/C2 in lung cancer tissue and the corresponding normal lung tissue,the correlation of MAGE-A3/C2 mRNA expression and clinical/biological factors of lung cancer were also analyzed.Eighty patients were enrolled in this study between October 2010 and October 2011,retrospective analysis was performed in long-term outcomes and prognostic factors,survival of patients was ascertained by telephone call to the patients or the patient's family.2?The MAGE-A3 siRNA interference fragments were synthesized by a chemical process,followed by transfecting lung cancer cells.The mRNA level of MAGE-A3 gene was detected by RT-PCR.Flow cytometry analyses?CCK-8?colony formation assay and transwell were performed to evaluate the effects of MAGE-A3 down-regulation on apoptosis?viability?migration and metastasis of lung cancer cells in vitro;Result1 MAGE-A3 and MAGE-C2 were frequently expressed in NSCLC tumor samples,but not expressed in corresponding normal lung tissue.2 The expression of MAGE-A3 was related to lymph node metastasis and late stage.3 MAGE-A3 positive patients had a poorer survival compared with negative patients.MAGE-A3 expression was a prognostic marker in NSCLC patients.4 The knockdown of MAGE-A3 tested did not exert effects on cell apoptosis and proliferation.5 Downregulating MAGE-A3 resulted in decreased colony-formation and migration ability of cancer cells.MAGE-A3 played a role on NSCLC matastasis through inducing epithelial-mesenchymal transition.ConclusionMAGE-A3 and MAGE-C2 were expressed with high frequencies in non-small cell lung cancer,the expression of MAGE-A3 could be served as an independent prognostic indicator.MAGE-A3 affect the epithelial mesenchymal transformation on tumor cells and was involved in invasion and metastasis of tumor cells.Canceer testis antigens could be used as potential targets for immunotherapy.