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Comprehensive Profiling Reveals Prognostic and Immunogenic Characteristics of Necroptosis in Soft Tissue Sarcomas

Soft tissue sarcomas (STSs) are heterogeneous malignancies derived from mesenchymal cells. Due to its rarity, heterogeneity, and limited overall response to chemotherapy, STSs represent a therapeutic challenge. Necroptosis is a novel therapeutic strategy for enhancing immunotherapy of cancer. Nevert...

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Detalles Bibliográficos
Autores principales: Qi, Lin, Xu, Ruiling, Ren, Xiaolei, Zhang, Wenchao, Yang, Zhimin, Tu, Chao, Li, Zhihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159500/
https://www.ncbi.nlm.nih.gov/pubmed/35663937
http://dx.doi.org/10.3389/fimmu.2022.877815
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author Qi, Lin
Xu, Ruiling
Ren, Xiaolei
Zhang, Wenchao
Yang, Zhimin
Tu, Chao
Li, Zhihong
author_facet Qi, Lin
Xu, Ruiling
Ren, Xiaolei
Zhang, Wenchao
Yang, Zhimin
Tu, Chao
Li, Zhihong
author_sort Qi, Lin
collection PubMed
description Soft tissue sarcomas (STSs) are heterogeneous malignancies derived from mesenchymal cells. Due to its rarity, heterogeneity, and limited overall response to chemotherapy, STSs represent a therapeutic challenge. Necroptosis is a novel therapeutic strategy for enhancing immunotherapy of cancer. Nevertheless, no research has explored the relationship between necroptosis-related genes (NRGs) and STSs. In this study, differentially expressed NRGs were identified using The Cancer Genome Atlas (TCGA) and The Cancer Genotype-Tissue Expression (GTEx) project. The expression levels of 34 NRGs were significantly different. Several key NRGs were validated using RT-qPCR and our own sequencing data. Patients with STSs were divided into two clusters using consensus cluster analysis, and significant differences were observed in their survival (p=0.002). We found the differentially expressed genes (DEGs) between the two clusters and carried out subsequent analysis. The necroptosis-related gene signatures with 10 key DEGs were identified with a risk score constructed. The prognosis of TCGA-SARC cohort with low necroptosis-related risk score was better (p<0.001). Meanwhile, the low-risk group had a significantly increased immune infiltration. Using the data of GSE17118 and another immunotherapy cohort as external validations, we observed significant survival differences between the two risk groups (p=0.019). The necroptosis-related risk score proved to be an independent prognostic factor, and a nomogram was further established and integrated with other clinical features. Notably, the necroptosis-related gene signature could also act as the prognostic indicator in other malignancies based on pan-cancer analysis. In summary, the study outlines NRGs in STSs and their potential role in prognosis and will be one of the important directions for future research.
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spelling pubmed-91595002022-06-02 Comprehensive Profiling Reveals Prognostic and Immunogenic Characteristics of Necroptosis in Soft Tissue Sarcomas Qi, Lin Xu, Ruiling Ren, Xiaolei Zhang, Wenchao Yang, Zhimin Tu, Chao Li, Zhihong Front Immunol Immunology Soft tissue sarcomas (STSs) are heterogeneous malignancies derived from mesenchymal cells. Due to its rarity, heterogeneity, and limited overall response to chemotherapy, STSs represent a therapeutic challenge. Necroptosis is a novel therapeutic strategy for enhancing immunotherapy of cancer. Nevertheless, no research has explored the relationship between necroptosis-related genes (NRGs) and STSs. In this study, differentially expressed NRGs were identified using The Cancer Genome Atlas (TCGA) and The Cancer Genotype-Tissue Expression (GTEx) project. The expression levels of 34 NRGs were significantly different. Several key NRGs were validated using RT-qPCR and our own sequencing data. Patients with STSs were divided into two clusters using consensus cluster analysis, and significant differences were observed in their survival (p=0.002). We found the differentially expressed genes (DEGs) between the two clusters and carried out subsequent analysis. The necroptosis-related gene signatures with 10 key DEGs were identified with a risk score constructed. The prognosis of TCGA-SARC cohort with low necroptosis-related risk score was better (p<0.001). Meanwhile, the low-risk group had a significantly increased immune infiltration. Using the data of GSE17118 and another immunotherapy cohort as external validations, we observed significant survival differences between the two risk groups (p=0.019). The necroptosis-related risk score proved to be an independent prognostic factor, and a nomogram was further established and integrated with other clinical features. Notably, the necroptosis-related gene signature could also act as the prognostic indicator in other malignancies based on pan-cancer analysis. In summary, the study outlines NRGs in STSs and their potential role in prognosis and will be one of the important directions for future research. Frontiers Media S.A. 2022-05-18 /pmc/articles/PMC9159500/ /pubmed/35663937 http://dx.doi.org/10.3389/fimmu.2022.877815 Text en Copyright © 2022 Qi, Xu, Ren, Zhang, Yang, Tu and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Qi, Lin
Xu, Ruiling
Ren, Xiaolei
Zhang, Wenchao
Yang, Zhimin
Tu, Chao
Li, Zhihong
Comprehensive Profiling Reveals Prognostic and Immunogenic Characteristics of Necroptosis in Soft Tissue Sarcomas
title Comprehensive Profiling Reveals Prognostic and Immunogenic Characteristics of Necroptosis in Soft Tissue Sarcomas
title_full Comprehensive Profiling Reveals Prognostic and Immunogenic Characteristics of Necroptosis in Soft Tissue Sarcomas
title_fullStr Comprehensive Profiling Reveals Prognostic and Immunogenic Characteristics of Necroptosis in Soft Tissue Sarcomas
title_full_unstemmed Comprehensive Profiling Reveals Prognostic and Immunogenic Characteristics of Necroptosis in Soft Tissue Sarcomas
title_short Comprehensive Profiling Reveals Prognostic and Immunogenic Characteristics of Necroptosis in Soft Tissue Sarcomas
title_sort comprehensive profiling reveals prognostic and immunogenic characteristics of necroptosis in soft tissue sarcomas
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159500/
https://www.ncbi.nlm.nih.gov/pubmed/35663937
http://dx.doi.org/10.3389/fimmu.2022.877815
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