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整合单细胞测序用于开发基于GJA4的黑色素瘤精准免疫预后模型。

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

作者信息

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

机构信息

Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui 230022, China; Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Hefei, Anhui 230022, China.

First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250000, China; Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250000, China.

出版信息

Transl Oncol. 2025 Sep;59:102450. doi: 10.1016/j.tranon.2025.102450. Epub 2025 Jul 9.

DOI:10.1016/j.tranon.2025.102450
PMID:40639089
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12275486/
Abstract

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.

摘要

方法

我们对从TCGA和GEO数据库获得的RNA测序（RNA-seq）和微阵列数据，以及GEO库中胶质瘤患者的单细胞RNA测序（scRNA-seq）数据进行了分析。这项综合研究通过实验研究得到加强，集中于探索肿瘤相关内皮细胞（TECs）与肿瘤之间的相互作用，以及阐明其中涉及的分子机制。

结果

单细胞测序分析确定了肿瘤相关内皮细胞内差异表达的基因。进一步研究突出了GJA4作为一个终末亚群的关键标记基因，其表达与不良预后相关。随后进行了实验以探索其潜在的功能机制。

结论

GJA4在黑色素瘤患者中高表达，其在肿瘤相关内皮细胞中的差异表达影响黑色素瘤的增殖和迁移。基于GJA4的风险模型有望成为个性化黑色素瘤治疗的预测和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/61f1b7a47a19/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/7483a4d1c2b1/gr1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/4f197c9f64bf/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/5b48fdd35843/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/a402f81c1673/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/8520fd6fa439/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/dd2ad1b05800/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/824be9c1ee08/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/172f99091fe7/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/61f1b7a47a19/gr10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/7483a4d1c2b1/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/2bc7cf58b3ae/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/4f197c9f64bf/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/5b48fdd35843/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/a402f81c1673/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/8520fd6fa439/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/dd2ad1b05800/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/824be9c1ee08/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/172f99091fe7/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a499/12275486/61f1b7a47a19/gr10.jpg

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本文引用的文献

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GJA4 expressed on cancer associated fibroblasts (CAFs)-A 'promoter' of the mesenchymal phenotype.在癌症相关成纤维细胞（CAFs）上表达的GJA4——间充质表型的一个“促进因子”
Transl Oncol. 2024 Aug;46:102009. doi: 10.1016/j.tranon.2024.102009. Epub 2024 Jun 4.
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Cutaneous melanoma.皮肤黑素瘤。
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A novel signature predicts prognosis and immunotherapy in lung adenocarcinoma based on cancer-associated fibroblasts.一种基于癌相关成纤维细胞的新型标志物可预测肺腺癌的预后和免疫治疗反应。
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Angiogenic signaling pathways and anti-angiogenic therapy for cancer.血管生成信号通路与癌症的抗血管生成治疗。
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Neoadjuvant Checkpoint Immunotherapy and Melanoma: The Time Is Now.新辅助检查点免疫治疗与黑色素瘤：现在正是时候。
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