Comprehensive Analysis to Identify MAGEA3 Expression Correlated With Immune Infiltrates and Lymph Node Metastasis in Gastric Cancer

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.

Identification and Validation of a Cancer-Testis Antigen-Related Signature to Predict the Prognosis in Stomach Adenocarcinoma

“…Validation using different methodologies demonstrated that the risk scores based on CTARSig were STAD-independent prognostic factors with good predictive finiteness and stability. Among the 11 CTA-related genes involved in the construction of CTARSig, MAGEA3 promotes the proliferation of GC cells and chemotherapy drug resistance [21] and is associated with lymph node metastasis and immune infiltration in GC [22]. In contrast, the upregulation of MAGEA11, a member of the MAGE family, in GC has been shown to be significantly associated with lower survival rates and immune infiltration, suggesting that MAGEA11 may be a potential biomarker and therapeutic target in GC [23].…”