CCL21 and CLDN11 Are Key Driving Factors of Lymph Node Metastasis in Gastric Cancer

Autor: Shaofei Yang MMed, Dandan Dong MMed, Xunxia Bao MS, Rongting Lu BS, Pufei Cheng BS, Sibo Zhu MD, Guanghua Yang MMed
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cancer Control, Vol 31 (2024)
Druh dokumentu: article
ISSN: 1526-2359
10732748
DOI: 10.1177/10732748241238616
Popis: Background Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. Understanding the molecular mechanisms of GC metastasis is crucial for improving patient survival outcomes. Methods RNA sequencing and analysis were performed on tissue samples from primary and lymph node metastatic lesions of gastric cancer. Differential gene analysis and functional pathway analysis were conducted. Immune infiltrating environment and protein expression levels were evaluated using immunohistochemistry. Cell experiments were conducted to investigate the role of CCL21 in GC metastasis. Results ACTG2, CNN1, DES, MUC6, and PGC were significantly upregulated in primary tumor cells, while CCL21, MS4A1, CR2, CLDN11, and FDCSP were significantly upregulated in metastatic tumor cells. Functional pathway analysis revealed enrichment in pathways related to immune response. CLDN11 and CCL21 were found to play important roles in promoting gastric cancer metastasis. Cell experiments confirmed the role of CCL21 in promoting GC cell growth and metastasis. CCL21 is highly expressed in GC tissues and binds to CCR7, leading to upregulation of CLDN11. This results in GC-lymph node metastasis and abnormal activation of immune cells (B cells and CD4 + T cells). Conclusion Inhibition of CCL21 and CLDN11 proteins may be a promising strategy for treating GC and preventing lymph node metastasis. These findings provide specific molecular markers for early lymph node metastases of GC, which can aid in developing treatment strategies and predicting patient prognosis.
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