JAM3: A prognostic biomarker for bladder cancer via epithelial–mesenchymal transition regulation

Authors

  • Zhong-qi Pang Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China https://orcid.org/0000-0002-5730-4967
  • Jian-she Wang Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China https://orcid.org/0000-0003-3032-9379
  • Jin-feng Wang Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China https://orcid.org/0000-0003-3935-0190
  • Ya-xuan Wang Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
  • Bo Ji Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
  • Yi-dan Xu Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China https://orcid.org/0000-0002-5550-9811
  • Jia-xin He Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
  • Lu Zhang Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
  • Li-qiu Zhang Teaching Experiment Center of Biotechnology, Harbin Medical University, Harbin, Heilongjiang, China
  • Bei-chen Ding Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
  • Yang Liu Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China; Department of Urology, The Eighth Affiliated Hospital of Sun Yat sen University, Shenzhen, Guangdong, China
  • Ming-hua Ren Department of Urology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China https://orcid.org/0009-0004-1602-5146

DOI:

https://doi.org/10.17305/bb.2024.9979

Keywords:

Junctional adhesion molecule 3 (JAM3), bladder cancer, epithelial–mesenchymal transition, prognostic biomarker, immune cell infiltration

Abstract

Understanding the intricate relationship between prognosis, immune function, and molecular markers in bladder cancer (BC) demands sophisticated analytical methods. To identify novel biomarkers for predicting prognosis and immune function in BC patients, we combined weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression analysis. This was conducted using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Ultimately, we screened the junctional adhesion molecule 3 (JAM3) as an independent risk factor in BC. High levels of JAM3 were linked to adverse clinical parameters, such as higher T and N stages. Additionally, a JAM3-based nomogram model accurately predicted 1-, 3- and 5-year survival rates of BC patients, indicating potential clinical utility. Functional enrichment analysis revealed that high JAM3 expression activated the calcium signaling pathway, the extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway, and was positively correlated with genes associated with epithelial–mesenchymal transition (EMT). Subsequently, we found that overexpression of JAM3 promoted the migration and invasion abilities in BC cells, regulating the expression levels of N-cadherin, matrix metallopeptidase 2 (MMP2), and Claudin-1 thereby promoting EMT levels. Additionally, we showed that JAM3 was negatively correlated with anti-tumor immune cells such as CD8+ T cells, while positively correlated with pro-tumor immune cells such as M2 macrophages, suggesting its involvement in immune cell infiltration. The immune checkpoint CD200 also showed a positive correlation with JAM3. Our findings revealed that elevated JAM3 levels are predictive of poor prognosis and immune cell infiltration in BC patients by regulating the EMT process.

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Published

23-02-2024

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Section

Molecular Biology

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How to Cite

1.
JAM3: A prognostic biomarker for bladder cancer via epithelial–mesenchymal transition regulation. Biomol Biomed [Internet]. 2024 Feb. 23 [cited 2024 Apr. 18];. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/9979