A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases

BackgroundUveal melanoma(UVM) is the most common intraocular malignancy and has a poor prognosis. The clinical significance of necroptosis(NCPS) in UVM is unclear.MethodsWe first identified necroptosis genes in UVM by single-cell analysis of the GSE139829 dataset from the GEO database and weighted c...

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Main Authors: Jiaheng Xie, Liang Chen, Qikai Tang, Wei Wei, Yuan Cao, Chuyan Wu, Jing Hang, Kai Zhang, Jingping Shi, Ming Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.847624/full
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author Jiaheng Xie
Liang Chen
Qikai Tang
Wei Wei
Yuan Cao
Chuyan Wu
Jing Hang
Kai Zhang
Jingping Shi
Ming Wang
author_facet Jiaheng Xie
Liang Chen
Qikai Tang
Wei Wei
Yuan Cao
Chuyan Wu
Jing Hang
Kai Zhang
Jingping Shi
Ming Wang
author_sort Jiaheng Xie
collection DOAJ
description BackgroundUveal melanoma(UVM) is the most common intraocular malignancy and has a poor prognosis. The clinical significance of necroptosis(NCPS) in UVM is unclear.MethodsWe first identified necroptosis genes in UVM by single-cell analysis of the GSE139829 dataset from the GEO database and weighted co-expression network analysis of TCGA data. COX regression and Lasso regression were used to construct the prognostic model. Then survival analysis, immune microenvironment analysis, and mutation analysis were carried out. Finally, cell experiments were performed to verify the role of ITPA in UVM.ResultBy necroptosis-related prognostic model, UVM patients in both TCGA and GEO cohorts could be classified as high-NCPS and low-NCPS groups, with significant differences in survival time between the two groups (P<0.001). Besides, the high-NCPS group had higher levels of immune checkpoint-related gene expression, suggesting that they might be more likely to benefit from immunotherapy. The cell experiments confirmed the role of ITPA, the most significant gene in the model, in UVM. After ITPA was knocked down, the activity, proliferation, and invasion ability of the MuM-2B cell line were significantly reduced.ConclusionOur study can provide a reference for the diagnosis and treatment of patients with UVM.
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spelling doaj.art-fed1ce7ae40c4b7ebf2786ddc2690e2e2022-12-21T17:24:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-02-011310.3389/fimmu.2022.847624847624A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public DatabasesJiaheng Xie0Liang Chen1Qikai Tang2Wei Wei3Yuan Cao4Chuyan Wu5Jing Hang6Kai Zhang7Jingping Shi8Ming Wang9Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, ChinaDepartment of General Surgery, Fuyang Hospital Affiliated to Anhui Medical University, Fuyang, ChinaDepartment of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, ChinaDepartment of General Surgery, Fuyang Hospital Affiliated to Anhui Medical University, Fuyang, ChinaFourth School of Clinical Medicine, Nanjing Medical University, Nanjing, ChinaRehabilitation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Ultrasound in Medicine, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, ChinaPancreas Center, The First Affiliated Hospital With Nanjing Medical University, Nanjing, ChinaDepartment of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, ChinaDepartment of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, ChinaBackgroundUveal melanoma(UVM) is the most common intraocular malignancy and has a poor prognosis. The clinical significance of necroptosis(NCPS) in UVM is unclear.MethodsWe first identified necroptosis genes in UVM by single-cell analysis of the GSE139829 dataset from the GEO database and weighted co-expression network analysis of TCGA data. COX regression and Lasso regression were used to construct the prognostic model. Then survival analysis, immune microenvironment analysis, and mutation analysis were carried out. Finally, cell experiments were performed to verify the role of ITPA in UVM.ResultBy necroptosis-related prognostic model, UVM patients in both TCGA and GEO cohorts could be classified as high-NCPS and low-NCPS groups, with significant differences in survival time between the two groups (P<0.001). Besides, the high-NCPS group had higher levels of immune checkpoint-related gene expression, suggesting that they might be more likely to benefit from immunotherapy. The cell experiments confirmed the role of ITPA, the most significant gene in the model, in UVM. After ITPA was knocked down, the activity, proliferation, and invasion ability of the MuM-2B cell line were significantly reduced.ConclusionOur study can provide a reference for the diagnosis and treatment of patients with UVM.https://www.frontiersin.org/articles/10.3389/fimmu.2022.847624/fulluveal melanomanecroptosisprognostic modelbioinformaticsITPA
spellingShingle Jiaheng Xie
Liang Chen
Qikai Tang
Wei Wei
Yuan Cao
Chuyan Wu
Jing Hang
Kai Zhang
Jingping Shi
Ming Wang
A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases
Frontiers in Immunology
uveal melanoma
necroptosis
prognostic model
bioinformatics
ITPA
title A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases
title_full A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases
title_fullStr A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases
title_full_unstemmed A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases
title_short A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases
title_sort necroptosis related prognostic model of uveal melanoma was constructed by single cell sequencing analysis and weighted co expression network analysis based on public databases
topic uveal melanoma
necroptosis
prognostic model
bioinformatics
ITPA
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.847624/full
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