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

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 explor...

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Main 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
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Translational Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S1936523325001810
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author Yantao Ding
Si Xie
Wenyang Nie
Yun Bai
Tianyu Yao
Yixiao Wang
Jiajie Chen
Bo Liang
Yi Zhou
Hui Cheng
Zaixing Wang
Shengxiu Liu
author_facet Yantao Ding
Si Xie
Wenyang Nie
Yun Bai
Tianyu Yao
Yixiao Wang
Jiajie Chen
Bo Liang
Yi Zhou
Hui Cheng
Zaixing Wang
Shengxiu Liu
author_sort Yantao Ding
collection DOAJ
description 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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series Translational Oncology
spelling doaj-art-a4cb2dbd7a534ecbb4c4ba1c3b2d9feb2025-08-20T03:17:46ZengElsevierTranslational Oncology1936-52332025-09-015910245010.1016/j.tranon.2025.102450Integrated single-cell sequencing for the development of a GJA4-based precision immuno-prognostic model in melanomaYantao Ding0Si Xie1Wenyang Nie2Yun Bai3Tianyu Yao4Yixiao Wang5Jiajie Chen6Bo Liang7Yi Zhou8Hui Cheng9Zaixing Wang10Shengxiu Liu11Department 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, ChinaDepartment 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, ChinaFirst Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250000, China; Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250000, ChinaDepartment of plastic surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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; Corresponding authors at: Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.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; Corresponding authors at: Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.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; Corresponding authors at: Department of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China.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.http://www.sciencedirect.com/science/article/pii/S1936523325001810MelanomaGJA4DiagnosisPrognosisTumor-associated endothelial cellsPersonalized therapy
spellingShingle Yantao Ding
Si Xie
Wenyang Nie
Yun Bai
Tianyu Yao
Yixiao Wang
Jiajie Chen
Bo Liang
Yi Zhou
Hui Cheng
Zaixing Wang
Shengxiu Liu
Integrated single-cell sequencing for the development of a GJA4-based precision immuno-prognostic model in melanoma
Translational Oncology
Melanoma
GJA4
Diagnosis
Prognosis
Tumor-associated endothelial cells
Personalized therapy
title Integrated single-cell sequencing for the development of a GJA4-based precision immuno-prognostic model in melanoma
title_full Integrated single-cell sequencing for the development of a GJA4-based precision immuno-prognostic model in melanoma
title_fullStr Integrated single-cell sequencing for the development of a GJA4-based precision immuno-prognostic model in melanoma
title_full_unstemmed Integrated single-cell sequencing for the development of a GJA4-based precision immuno-prognostic model in melanoma
title_short Integrated single-cell sequencing for the development of a GJA4-based precision immuno-prognostic model in melanoma
title_sort integrated single cell sequencing for the development of a gja4 based precision immuno prognostic model in melanoma
topic Melanoma
GJA4
Diagnosis
Prognosis
Tumor-associated endothelial cells
Personalized therapy
url http://www.sciencedirect.com/science/article/pii/S1936523325001810
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