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

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.

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Lymph node metastasis-derived gastric cancer cells educate bone marrow-derived mesenchymal stem cells via YAP signaling activation by exosomal Wnt5a

Oncogene ◽

10.1038/s41388-021-01722-8 ◽

2021 ◽

Vol 40 (12) ◽

pp. 2296-2308

Author(s):

Mei Wang ◽

Xinxin Zhao ◽

Rong Qiu ◽

Zheng Gong ◽

Feng Huang ◽

...

Keyword(s):

Gastric Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Metastatic Gastric Cancer ◽

Gastric Cancer Cells ◽

Node Metastasis ◽

Signaling Activation

AbstractLymph node metastasis (LNM), a common metastatic gastric-cancer (GC) route, is closely related to poor prognosis in GC patients. Bone marrow-derived mesenchymal stem cells (BM-MSCs) preferentially engraft at metastatic lesions. Whether BM-MSCs are specifically reprogrammed by LNM-derived GC cells (LNM-GCs) and incorporated into metastatic LN microenvironment to prompt GC malignant progression remains unknown. Herein, we found that LNM-GCs specifically educated BM-MSCs via secretory exosomes. Exosomal Wnt5a was identified as key protein mediating LNM-GCs education of BM-MSCs, which was verified by analysis of serum exosomes collected from GC patients with LNM. Wnt5a-enriched exosomes induced YAP dephosphorylation in BM-MSCs, whereas Wnt5a-deficient exosomes exerted the opposite effect. Inhibition of YAP signaling by verteporfin blocked LNM-GC exosome- and serum exosome-mediated reprogramming in BM-MSCs. Analysis of MSC-like cells obtained from metastatic LN tissues of GC patients (GLN-MSCs) confirmed that BM-MSCs incorporated into metastatic LN microenvironment, and that YAP activation participated in maintaining their tumor-promoting phenotype and function. Collectively, our results show that LNM-GCs specifically educated BM-MSCs via exosomal Wnt5a-elicited activation of YAP signaling. This study provides new insights into the mechanisms of LNM in GC and BM-MSC reprogramming, and will provide potential therapeutic targets and detection indicators for GC patients with LNM.

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Evaluation of lymph node metastasis in patients with gastric cancer: a comparison of the directionality of lymph node metastasis and the total number of metastatic lymph nodes

Surgery Today ◽

10.1007/s00595-012-0454-8 ◽

2012 ◽

Vol 43 (2) ◽

pp. 130-135 ◽

Cited By ~ 3

Author(s):

Maki Kitagawa ◽

Daisuke Ichikawa ◽

Shuhei Komatsu ◽

Kazuma Okamoto ◽

Atsushi Shiozaki ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Lymph Nodes ◽

Metastatic Lymph Nodes ◽

Node Metastasis ◽

Metastatic Lymph

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Predictive factors for lymph node metastasis in additional gastrectomy after endoscopic resection of cT1aN0 gastric cancer

Surgery Today ◽

10.1007/s00595-015-1281-5 ◽

2015 ◽

Vol 46 (9) ◽

pp. 1031-1038 ◽

Cited By ~ 7

Author(s):

Satoru Ishii ◽

Keishi Yamashita ◽

Hiroshi Kato ◽

Nobuyuki Nishizawa ◽

Hideki Ushiku ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Endoscopic Resection ◽

Predictive Factors ◽

Node Metastasis ◽

Additional Gastrectomy

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miR-21 Is a Promising Novel Biomarker for Lymph Node Metastasis in Patients with Gastric Cancer

Gastroenterology Research and Practice ◽

10.1155/2012/640168 ◽

2012 ◽

Vol 2012 ◽

pp. 1-5 ◽

Cited By ~ 18

Author(s):

Yuejuan Xu ◽

Jue Sun ◽

Jianhua Xu ◽

Qi Li ◽

Yuewu Guo ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Malignant Disease ◽

Close Association ◽

Survival Rates ◽

Expression Level ◽

Human Gastric Cancer ◽

Node Metastasis ◽

Kaplan Meier

Background. Gastric cancer (GC) is an important malignant disease around the world. Abnormalities of microRNAs (miRNAs) have been implicated in carcinogenesis of various cancers. In the present study, we examined miR-21 expression in human gastric cancer with lymph node metastasis and attempted to uncover its relationship with clinicopathologic data, especially with lymph node metastasis.Materials and Methods. The expression levels of miR-21 in the tumor specimens of GC patients were quantified by RT-PCR. The correlation between miR-21 level and multiple clinicopathological factors was then examined by Mann-Whitney test, Kaplan-Meier survival analysis, and operating characteristic (ROC) analysis.Results. The expression level of miR-21 was higher in GC patients with lymph node metastasis than in those without lymph node metastasis (P<0.05). Expression level of miR-21 was significantly correlated with histologic type, T stage, lymph node metastasis and pTNM stage. The overall survival rates in GC patients with low upregulated miR-21 expression were significantly higher than those with high upregulated miR-21 (P<0.05).Conclusion. A close association is implicated between the elevated miR-21and lymph node metastasis, which could potentially be exploited as a practical biomarker for lymph node metastasis in patients with GC.

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