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2000
Volume 26, Issue 2
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Introduction

Laryngeal cancer is a common malignant tumor of the head and neck worldwide. This study aimed to identify potential risk genes, with a particular focus on GPR65, and to investigate its functional mechanism in pathogenesis of laryngeal cancer.

Materials and Methods

Comprehensive analyses, including scRNA-seq analysis, genome-wide association study (GWAS), eQTL, and TCGA data, were conducted to identify risk genes for laryngeal cancer and characterize the function of these risk genes. Next, qRT-PCR, immunohistochemistry, cell proliferation, cell migration, and invasion assays were employed to verify the expression of GPR65 and its function in laryngeal squamous cell carcinoma (LSCC) .

Results

Single-cell analysis screened 416 highly expressed genes in CD8+ central memory T cells (CD8_CM). Mendelian randomization (MR) analysis identified GPR65 as a crucial gene in the development of laryngeal cancer. GPR65 expression was significantly elevated in the tumor tissues compared to normal tissues, with particularly high levels observed in stage IV HNSCC. , LSCC cell lines (TU686 and Hep-2) exhibited marked upregulation of GPR65 relative to normal epithelial cells, and siRNA-mediated silencing of GPR65 suppressed the proliferation, migration, and invasion of LSCC cells. Furthermore, GPR65 expression showed a positive correlation with immune cell infiltration, particularly CD8+ T cells and M1 macrophages.

Discussion

This study identified GPR65 as a potential risk gene for laryngeal cancer through single-cell transcriptomics and MR analyses and provided novel evidence of its involvement in the development of the cancer.

Conclusion

The present findings showed that highly expressed GPR65 was a tumor-promoting gene in laryngeal cancer, showing its clinical value as a potential therapeutic target.

© 2026 Bentham Science Publishers
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GPR65 as a Laryngeal Cancer Risk Gene Identified through Single-Cell Transcriptomics, Mendelian Randomization Analysis, and Experimental Validation
Anti-Cancer Agents in Medicinal Chemistry 26, 202 (2026); https://doi.org/10.2174/0118715206414176250905114930
/content/journals/acamc/10.2174/0118715206414176250905114930
/content/journals/acamc/10.2174/0118715206414176250905114930
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  • Article Type:     Research Article
Keyword(s): central memory CD8+ T cells; Genome-wide association study; GPR65; Laryngeal cancer; Mendelian randomization (MR) analysis; single-cell transcriptomic sequencing

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