A Novel Necroptosis-Related Gene Signature in Skin Cutaneous Melanoma Prognosis and Tumor Microenvironment

Background: Necroptosis has been identified recently as a newly recognized programmed cell death that has an impact on tumor progression and prognosis, although the necroptosis-related gene (NRGs) potential prognostic value in skin cutaneous melanoma (SKCM) has not been identified. The aim of this s...

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Main Authors: Binyu Song, Pingfan Wu, Zhen Liang, Jianzhang Wang, Yu Zheng, Yuanyong Wang, Hao Chi, Zichao Li, Yajuan Song, Xisheng Yin, Zhou Yu, Baoqiang Song
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2022.917007/full
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author Binyu Song
Pingfan Wu
Zhen Liang
Jianzhang Wang
Yu Zheng
Yuanyong Wang
Hao Chi
Zichao Li
Yajuan Song
Xisheng Yin
Zhou Yu
Baoqiang Song
author_facet Binyu Song
Pingfan Wu
Zhen Liang
Jianzhang Wang
Yu Zheng
Yuanyong Wang
Hao Chi
Zichao Li
Yajuan Song
Xisheng Yin
Zhou Yu
Baoqiang Song
author_sort Binyu Song
collection DOAJ
description Background: Necroptosis has been identified recently as a newly recognized programmed cell death that has an impact on tumor progression and prognosis, although the necroptosis-related gene (NRGs) potential prognostic value in skin cutaneous melanoma (SKCM) has not been identified. The aim of this study was to construct a prognostic model of SKCM through NRGs in order to help SKCM patients obtain precise clinical treatment strategies.Methods: RNA sequencing data collected from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed and prognostic NRGs in SKCM. Depending on 10 NRGs via the univariate Cox regression analysis usage and LASSO algorithm, the prognostic risk model had been built. It was further validated by the Gene Expression Omnibus (GEO) database. The prognostic model performance had been assessed using receiver operating characteristic (ROC) curves. We evaluated the predictive power of the prognostic model for tumor microenvironment (TME) and immunotherapy response.Results: We constructed a prognostic model based on 10 NRGs (FASLG, TLR3, ZBP1, TNFRSF1B, USP22, PLK1, GATA3, EGFR, TARDBP, and TNFRSF21) and classified patients into two high- and low-risk groups based on risk scores. The risk score was considered a predictive factor in the two risk groups regarding the Cox regression analysis. A predictive nomogram had been built for providing a more beneficial prognostic indicator for the clinic. Functional enrichment analysis showed significant enrichment of immune-related signaling pathways, a higher degree of immune cell infiltration in the low-risk group than in the high-risk group, a negative correlation between risk scores and most immune checkpoint inhibitors (ICIs), anticancer immunity steps, and a more sensitive response to immunotherapy in the low-risk group.Conclusions: This risk score signature could be applied to assess the prognosis and classify low- and high-risk SKCM patients and help make the immunotherapeutic strategy decision.
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spelling doaj.art-362f096c8ad74a8c85517a95219bc6282022-12-22T03:42:14ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-07-011310.3389/fgene.2022.917007917007A Novel Necroptosis-Related Gene Signature in Skin Cutaneous Melanoma Prognosis and Tumor MicroenvironmentBinyu Song0Pingfan Wu1Zhen Liang2Jianzhang Wang3Yu Zheng4Yuanyong Wang5Hao Chi6Zichao Li7Yajuan Song8Xisheng Yin9Zhou Yu10Baoqiang Song11Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, ChinaDepartment of Burn and Plastic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, ChinaDepartment of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, ChinaHospital for Skin Disease (Institute of Dermatology), Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, ChinaDepartment of Thoracic Surgery, Tangdu Hospital of Air Force Military Medical University, Xi'an, ChinaClinical Medical College, Southwest Medical University, Luzhou, ChinaDepartment of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, ChinaDepartment of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, ChinaClinical Medical College, Southwest Medical University, Luzhou, ChinaDepartment of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, ChinaDepartment of Plastic Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, ChinaBackground: Necroptosis has been identified recently as a newly recognized programmed cell death that has an impact on tumor progression and prognosis, although the necroptosis-related gene (NRGs) potential prognostic value in skin cutaneous melanoma (SKCM) has not been identified. The aim of this study was to construct a prognostic model of SKCM through NRGs in order to help SKCM patients obtain precise clinical treatment strategies.Methods: RNA sequencing data collected from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed and prognostic NRGs in SKCM. Depending on 10 NRGs via the univariate Cox regression analysis usage and LASSO algorithm, the prognostic risk model had been built. It was further validated by the Gene Expression Omnibus (GEO) database. The prognostic model performance had been assessed using receiver operating characteristic (ROC) curves. We evaluated the predictive power of the prognostic model for tumor microenvironment (TME) and immunotherapy response.Results: We constructed a prognostic model based on 10 NRGs (FASLG, TLR3, ZBP1, TNFRSF1B, USP22, PLK1, GATA3, EGFR, TARDBP, and TNFRSF21) and classified patients into two high- and low-risk groups based on risk scores. The risk score was considered a predictive factor in the two risk groups regarding the Cox regression analysis. A predictive nomogram had been built for providing a more beneficial prognostic indicator for the clinic. Functional enrichment analysis showed significant enrichment of immune-related signaling pathways, a higher degree of immune cell infiltration in the low-risk group than in the high-risk group, a negative correlation between risk scores and most immune checkpoint inhibitors (ICIs), anticancer immunity steps, and a more sensitive response to immunotherapy in the low-risk group.Conclusions: This risk score signature could be applied to assess the prognosis and classify low- and high-risk SKCM patients and help make the immunotherapeutic strategy decision.https://www.frontiersin.org/articles/10.3389/fgene.2022.917007/fullnecroptosisprognostic signatureSKCMTCGATME
spellingShingle Binyu Song
Pingfan Wu
Zhen Liang
Jianzhang Wang
Yu Zheng
Yuanyong Wang
Hao Chi
Zichao Li
Yajuan Song
Xisheng Yin
Zhou Yu
Baoqiang Song
A Novel Necroptosis-Related Gene Signature in Skin Cutaneous Melanoma Prognosis and Tumor Microenvironment
Frontiers in Genetics
necroptosis
prognostic signature
SKCM
TCGA
TME
title A Novel Necroptosis-Related Gene Signature in Skin Cutaneous Melanoma Prognosis and Tumor Microenvironment
title_full A Novel Necroptosis-Related Gene Signature in Skin Cutaneous Melanoma Prognosis and Tumor Microenvironment
title_fullStr A Novel Necroptosis-Related Gene Signature in Skin Cutaneous Melanoma Prognosis and Tumor Microenvironment
title_full_unstemmed A Novel Necroptosis-Related Gene Signature in Skin Cutaneous Melanoma Prognosis and Tumor Microenvironment
title_short A Novel Necroptosis-Related Gene Signature in Skin Cutaneous Melanoma Prognosis and Tumor Microenvironment
title_sort novel necroptosis related gene signature in skin cutaneous melanoma prognosis and tumor microenvironment
topic necroptosis
prognostic signature
SKCM
TCGA
TME
url https://www.frontiersin.org/articles/10.3389/fgene.2022.917007/full
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