Abstract
A variety of melanoma-associated antigen-A (MAGE-A) protein are commonly detected in lung cancers. Their biological function is not well characterized but may involve cell cycle progression and the regulation of apoptosis. We hypothesized that MAGE-A9 is involved in the regulation of apoptosis. To test this hypothesis, we evaluated MAGE-A9 protein expression by immunohistochemical staining and we assessed the relationship between the expression of MAGE-A9 and clinical pathological parameters. In addition, we investigated the effect of MAGE-A9 down-regulation in lung adenocarcinoma. The results showed that a high expression level of MAGE-A9 protein in lung adenocarcinoma tumor cells was related to larger tumor diameter (P = 0.013) and poor differentiation (P = 0.029). Cox regression analysis revealed that the expression of MAGE-A9 in lung adenocarcinoma tumor cells (P < 0.001) is an independent prognostic factor in five-year survival rates. NSCLC cells with silenced MAGE-A9 had decreased cell proliferation, migration and invasion in cell culture compared to corresponding control cells. The NSCLC cells showing down-regulated MAGE-A9 induced the expression of apoptosis-associated proteins. In addition, MAGE-A9 was associated with resistance to conventional chemotherapeutic agents. Our findings provide evidence that MAGE-A9 could be a potential therapeutic target in NSCLC.
Highlights
Lung cancer is the most frequently occurring type of cancer and is the leading cause of cancer deaths worldwide
Our previous research showed high expression of MAGE-A9 in tumor and stromal cells of non-small cell lung correlates with poor survival [35]
High MAGE-A9 expression was detected in 42.78% of lung adenocarcinoma tissues (77/180) compared to 22.34% of matched tumor-adjacent tissues (21/94) (χ2 = 11.226, P = 0.001)
Summary
Lung cancer is the most frequently occurring type of cancer and is the leading cause of cancer deaths worldwide. Lung cancer can be divided into two types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) [1,2,3]. The prognosis for NSCLC patients is highly dependent on the stage at diagnosis. Despite efforts to develop early screening tools, a majority of tumors are detected at an advanced stage, and approximately 85% of these cancers are identified as NSCLC [3,4]. Multi-model treatment strategies including surgery, chemotherapy, radiotherapy and immunotherapy are used, the prognosis of these patients remains poor, with a 5-year overall survival rate of approximately 10% and a median survival time of 16 to 18 months [2, 5]. With recent developments in gene transfer technology, gene- targeted therapy is expected to become the good treatment for NSCLC [6]. It is necessary to explore novel biological molecular markers for predicting the progression of NSCLC and aiding targeted therapy
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