Abstract
Gastric cancer (GC) is an aggressive malignant tumor and causes a significant number of deaths every year. With the coming of the age of cancer immunotherapy, search for a new target in gastric cancer may benefit more advanced patients. Melanoma-associated antigen-A3 (MAGEA3), one of the members of the cancer-testis antigen (CTA) family, was considered an important part of cancer immunotherapy. We evaluate the potential role of MAGEA3 in GC through the TCGA database. The result revealed that MAGEA3 is upregulated in GC and linked to poor OS and lymph node metastasis. MAGEA3 was also correlated with immune checkpoints, TMB, and affected the tumor immune microenvironment and the prognosis of GC through CIBERSORT, TIMER, and Kaplan-Meier plotter database analysis. In addition, GSEA-identified MAGEA3 is involved in the immune regulation of GC. Moreover, the protein-protein interaction (PPI) networks of MAGEA3 were constructed through STRING database and MAGEA3-correlated miRNAs were screened based on the joint analysis of multiple databases. In terms of experimental verification, we constructed pET21a (+)/MAGEA3 restructuring plasmids and transformed to Escherichia coli Rosetta. MAGEA3 protein was used as an antigen after being expressed and purified and can effectively detect the specific IgG in 93 GC patients’ serum specimens with 44.08% sensitivity and 92.54% specificity. Through further analysis, the positive rate of MAGEA3 was related to the stage and transfer number of lymph nodes. These results indicated that MAGEA3 is a novel biomarker and correlated with lymph node metastasis and immune infiltrates in GC, which could be a new target for immunotherapy.
Highlights
Gastric cancer (GC) is an aggressive and devastating disease, with more than 1 million new cases a year, and remains the fourth cause of cancer-related death, the mortality and mortality were declining gradually [1]
Since Melanoma-associated antigen-A3 (MAGEA3) is abnormally highly expressed in tumor sample, we subsequently investigated the influence of MAGEA3 expression on GC patients’ prognosis and clinicopathology
According to prognostic results from the TIMER database and Kaplan-Meier plotter database (Figure 1C), our results indicated that higher expression of MAGEA3 associated with poorer overall survival (OS) in GC patients (p < 0.05)
Summary
Gastric cancer (GC) is an aggressive and devastating disease, with more than 1 million new cases a year, and remains the fourth cause of cancer-related death, the mortality and mortality were declining gradually [1]. Carcinoembryonic antigens including CEA and CA199 are the most widely used gastric cancer detection markers in clinical practice [9, 10] These markers lack the sensitivity and specificity needed to assess the diagnosis and prognosis of gastric cancer; many other tumor markers have been discovered and proved their potential efficacy as diagnostic and prognostic tools in gastric cancer. These markers are having problems, such as, insufficient sensitivity that needs further clinical verification [11]. The purpose of this study is to find a target that plays a role in detection and immunotherapy
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