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Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer
Necroptosis is a novel type of regulated cell death that is intimately associated with a variety of tumors. However, how necroptosis affects the identification of gastric cancer (GC) remains unclear. Here we seek to find new potential necroptosis-related biomarkers to predict GC prognosis and immuno...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504871/ https://www.ncbi.nlm.nih.gov/pubmed/36159818 http://dx.doi.org/10.3389/fimmu.2022.977338 |
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author | Xia, Yan Zhang, Rongzheng Wang, Mingzhu Li, Jiaqi Dong, Jianming He, Kaitong Guo, Ting Ju, Xiaomei Ru, Jiaqiu Zhang, Shuyun Sun, Yihua |
author_facet | Xia, Yan Zhang, Rongzheng Wang, Mingzhu Li, Jiaqi Dong, Jianming He, Kaitong Guo, Ting Ju, Xiaomei Ru, Jiaqiu Zhang, Shuyun Sun, Yihua |
author_sort | Xia, Yan |
collection | PubMed |
description | Necroptosis is a novel type of regulated cell death that is intimately associated with a variety of tumors. However, how necroptosis affects the identification of gastric cancer (GC) remains unclear. Here we seek to find new potential necroptosis-related biomarkers to predict GC prognosis and immunotherapy effect. We used Cox analysis to obtain shared prognostic markers related to necroptosis from five datasets (TCGA and four GEO datasets). Then, a necroptosis-related gene prognostic score (NRGPS) system was constructed using LASSO Cox regression, NRGPS consisting of three necroptosis-related mRNAs (AXL, RAI14, and NOX4) was identified, 31 pairs of GC and adjacent normal tissues from the Second Hospital of Harbin Medical University were collected and Real-Time Quantitative PCR (RT-qPCR) was used to detect the relative expression levels of the three necroptosis-related mRNAs, and external validation was performed on four GEO datasets (GSE84437, GSE26901, GSE62254 and GSE15459). In this study, Overall survival (OS) in the high-NRGPS group was significantly lower than in the low-NRGPS group. Cox regression analyses showed that NRGPS was an independent prognostic variable. Tumor-mutation-burden (TMB), tumor microenvironment (TME), microsatellite instability (MSI), and Tumor Immune Dysfunction and Exclusion (TIDE) scoring were used as predictors of the immunotherapy response. A cancer-friendly immune microenvironment, a high TIDE score, a low TMB, and a low MSI were all characteristics of the high-NRGPS group, and they all consistently showed that the issues seen there are related to immune escape in GC. The combination of three candidate genes may be an effective method for diagnostic assessment of GC prognosis and immunotherapy efficacy. |
format | Online Article Text |
id | pubmed-9504871 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95048712022-09-24 Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer Xia, Yan Zhang, Rongzheng Wang, Mingzhu Li, Jiaqi Dong, Jianming He, Kaitong Guo, Ting Ju, Xiaomei Ru, Jiaqiu Zhang, Shuyun Sun, Yihua Front Immunol Immunology Necroptosis is a novel type of regulated cell death that is intimately associated with a variety of tumors. However, how necroptosis affects the identification of gastric cancer (GC) remains unclear. Here we seek to find new potential necroptosis-related biomarkers to predict GC prognosis and immunotherapy effect. We used Cox analysis to obtain shared prognostic markers related to necroptosis from five datasets (TCGA and four GEO datasets). Then, a necroptosis-related gene prognostic score (NRGPS) system was constructed using LASSO Cox regression, NRGPS consisting of three necroptosis-related mRNAs (AXL, RAI14, and NOX4) was identified, 31 pairs of GC and adjacent normal tissues from the Second Hospital of Harbin Medical University were collected and Real-Time Quantitative PCR (RT-qPCR) was used to detect the relative expression levels of the three necroptosis-related mRNAs, and external validation was performed on four GEO datasets (GSE84437, GSE26901, GSE62254 and GSE15459). In this study, Overall survival (OS) in the high-NRGPS group was significantly lower than in the low-NRGPS group. Cox regression analyses showed that NRGPS was an independent prognostic variable. Tumor-mutation-burden (TMB), tumor microenvironment (TME), microsatellite instability (MSI), and Tumor Immune Dysfunction and Exclusion (TIDE) scoring were used as predictors of the immunotherapy response. A cancer-friendly immune microenvironment, a high TIDE score, a low TMB, and a low MSI were all characteristics of the high-NRGPS group, and they all consistently showed that the issues seen there are related to immune escape in GC. The combination of three candidate genes may be an effective method for diagnostic assessment of GC prognosis and immunotherapy efficacy. Frontiers Media S.A. 2022-08-26 /pmc/articles/PMC9504871/ /pubmed/36159818 http://dx.doi.org/10.3389/fimmu.2022.977338 Text en Copyright © 2022 Xia, Zhang, Wang, Li, Dong, He, Guo, Ju, Ru, Zhang and Sun 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 Xia, Yan Zhang, Rongzheng Wang, Mingzhu Li, Jiaqi Dong, Jianming He, Kaitong Guo, Ting Ju, Xiaomei Ru, Jiaqiu Zhang, Shuyun Sun, Yihua Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer |
title | Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer |
title_full | Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer |
title_fullStr | Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer |
title_full_unstemmed | Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer |
title_short | Development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer |
title_sort | development and validation of a necroptosis-related gene prognostic score to predict prognosis and efficiency of immunotherapy in gastric cancer |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504871/ https://www.ncbi.nlm.nih.gov/pubmed/36159818 http://dx.doi.org/10.3389/fimmu.2022.977338 |
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