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

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

PMC · DOI: 10.1016/j.tranon.2025.102450 · 2025-07-09

## TL;DR

This study explores how GJA4 in tumor-associated endothelial cells affects melanoma progression and could help develop personalized treatment models.

## Contribution

The study introduces a novel GJA4-based immuno-prognostic model for melanoma using single-cell sequencing and multi-omics data.

## Key findings

- GJA4 is significantly differentially expressed in tumor-associated endothelial cells and is linked to poor prognosis.
- GJA4 expression may inhibit CD8+ T cell accumulation in the tumor microenvironment.
- GJA4-based risk models show potential as predictive and therapeutic targets for melanoma treatment.

## Abstract

•Endothelial cell play an essential role in tumor microenvironment of melanoma.•2.GJA4 Significantly differentially expressed in tumor-associated endothelial cell.•GJA4 expression in tumor endothelial cells may inhibit the accumulation of CD8+ T cells.

Endothelial cell play an essential role in tumor microenvironment of melanoma.

2.GJA4 Significantly differentially expressed in tumor-associated endothelial cell.

GJA4 expression in tumor endothelial cells may inhibit the accumulation of CD8+ T cells.

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.

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.

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.

## Linked entities

- **Genes:** GJA4 (gap junction protein alpha 4) [NCBI Gene 2701]
- **Diseases:** melanoma (MONDO:0005105)

## Full-text entities

- **Genes:** GJA4 (gap junction protein alpha 4) [NCBI Gene 2701] {aka CX37}
- **Diseases:** glioma (MESH:D005910), melanoma (MESH:D008545), tumor (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

16 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12275486/full.md

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Source: https://tomesphere.com/paper/PMC12275486