Translational Oncology (Sep 2025)

Integrated single-cell sequencing for the development of a GJA4-based precision immuno-prognostic model in melanoma

  • Yantao Ding,
  • Si Xie,
  • Wenyang Nie,
  • Yun Bai,
  • Tianyu Yao,
  • Yixiao Wang,
  • Jiajie Chen,
  • Bo Liang,
  • Yi Zhou,
  • Hui Cheng,
  • Zaixing Wang,
  • Shengxiu Liu

DOI
https://doi.org/10.1016/j.tranon.2025.102450
Journal volume & issue
Vol. 59
p. 102450

Abstract

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Methods: We conducted an analysis of RNA-seq and microarray data obtained from the TCGA and GEO databases, alongside single-cell RNA sequencing (scRNA-seq) data from glioma patients within the GEO repository. This comprehensive investigation, augmented by experimental studies, concentrated on exploring the interactions between tumor-associated endothelial cells (TECs) and tumors, as well as elucidating the molecular mechanisms involved. Results: Single-cell sequencing analysis identified differentially expressed genes within tumor-associated endothelial cells. Further investigation highlighted GJA4 as a pivotal marker gene for a terminal subpopulation, with its expression linked to poor prognosis. Subsequent experiments were conducted to explore its underlying functional mechanisms. Conclusions: GJA4 is highly expressed in melanoma patients, and its differential expression in tumor-associated endothelial cells influences melanoma proliferation and migration. GJA4-based risk models hold potential as predictive and therapeutic targets for personalized melanoma treatment.

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