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A Novel Ferroptosis-Related Gene Risk Signature for Predicting Prognosis and Immunotherapy Response in Gastric Cancer
BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer death worldwide with complicated molecular and cellular heterogeneity. Iron metabolism and ferroptosis play crucial roles in the pathogenesis of GC. However, the prognostic role and immunotherapy biomarker potential of ferroptosis-...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642032/ https://www.ncbi.nlm.nih.gov/pubmed/34868391 http://dx.doi.org/10.1155/2021/2385406 |
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author | Liu, Shi-jin Yang, Ya-bing Zhou, Jia-xin Lin, Yu-jian Pan, Yun-long Pan, Jing-hua |
author_facet | Liu, Shi-jin Yang, Ya-bing Zhou, Jia-xin Lin, Yu-jian Pan, Yun-long Pan, Jing-hua |
author_sort | Liu, Shi-jin |
collection | PubMed |
description | BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer death worldwide with complicated molecular and cellular heterogeneity. Iron metabolism and ferroptosis play crucial roles in the pathogenesis of GC. However, the prognostic role and immunotherapy biomarker potential of ferroptosis-related genes (FRGs) in GC still remains to be clarified. METHODS: We comprehensively analyzed the prognosis of different expression FRGs, based on gastric carcinoma patients in the TCGA cohort. The functional enrichment and immune microenvironment associated with these genes in gastric cancer were investigated. The prognostic model was constructed to clarify the relation between FRGs and the prognosis of GC. Meanwhile, the ceRNA network of FRGs in the prognostic model was performed to explore the regulatory mechanisms. RESULTS: Gastric carcinoma patients were classified into the A, B, and C FRGClusters with different features based on 19 prognostic ferroptosis-related differentially expressed genes in the TCGA database. To quantify the FRG characteristics of individual patients, FRGScore was constructed. And the research shows the GC patients with higher FRGScore had worse survival outcome. Moreover, thirteen prognostic ferroptosis-related differentially expressed genes (DEGs) were selected to construct a prognostic model for GC survival outcome with a superior accuracy in this research. And we also found that FRG RiskScore can be an independent biomarker for the prognosis of GC patients. Interestingly, GC patients with lower RiskScore had less immune dysfunction and were more likely to respond to immunotherapy according to TIDE value analysis. Finally, a ceRNA network based on FRGs in the prognostic model was analyzed to show the concrete regulation mechanisms. CONCLUSIONS: The ferroptosis-related gene risk signature has a superior potent in predicting GC prognosis and acts as the biomarkers for immunotherapy, which may provide a reference in clinic. |
format | Online Article Text |
id | pubmed-8642032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-86420322021-12-04 A Novel Ferroptosis-Related Gene Risk Signature for Predicting Prognosis and Immunotherapy Response in Gastric Cancer Liu, Shi-jin Yang, Ya-bing Zhou, Jia-xin Lin, Yu-jian Pan, Yun-long Pan, Jing-hua Dis Markers Research Article BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer death worldwide with complicated molecular and cellular heterogeneity. Iron metabolism and ferroptosis play crucial roles in the pathogenesis of GC. However, the prognostic role and immunotherapy biomarker potential of ferroptosis-related genes (FRGs) in GC still remains to be clarified. METHODS: We comprehensively analyzed the prognosis of different expression FRGs, based on gastric carcinoma patients in the TCGA cohort. The functional enrichment and immune microenvironment associated with these genes in gastric cancer were investigated. The prognostic model was constructed to clarify the relation between FRGs and the prognosis of GC. Meanwhile, the ceRNA network of FRGs in the prognostic model was performed to explore the regulatory mechanisms. RESULTS: Gastric carcinoma patients were classified into the A, B, and C FRGClusters with different features based on 19 prognostic ferroptosis-related differentially expressed genes in the TCGA database. To quantify the FRG characteristics of individual patients, FRGScore was constructed. And the research shows the GC patients with higher FRGScore had worse survival outcome. Moreover, thirteen prognostic ferroptosis-related differentially expressed genes (DEGs) were selected to construct a prognostic model for GC survival outcome with a superior accuracy in this research. And we also found that FRG RiskScore can be an independent biomarker for the prognosis of GC patients. Interestingly, GC patients with lower RiskScore had less immune dysfunction and were more likely to respond to immunotherapy according to TIDE value analysis. Finally, a ceRNA network based on FRGs in the prognostic model was analyzed to show the concrete regulation mechanisms. CONCLUSIONS: The ferroptosis-related gene risk signature has a superior potent in predicting GC prognosis and acts as the biomarkers for immunotherapy, which may provide a reference in clinic. Hindawi 2021-11-26 /pmc/articles/PMC8642032/ /pubmed/34868391 http://dx.doi.org/10.1155/2021/2385406 Text en Copyright © 2021 Shi-jin Liu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Liu, Shi-jin Yang, Ya-bing Zhou, Jia-xin Lin, Yu-jian Pan, Yun-long Pan, Jing-hua A Novel Ferroptosis-Related Gene Risk Signature for Predicting Prognosis and Immunotherapy Response in Gastric Cancer |
title | A Novel Ferroptosis-Related Gene Risk Signature for Predicting Prognosis and Immunotherapy Response in Gastric Cancer |
title_full | A Novel Ferroptosis-Related Gene Risk Signature for Predicting Prognosis and Immunotherapy Response in Gastric Cancer |
title_fullStr | A Novel Ferroptosis-Related Gene Risk Signature for Predicting Prognosis and Immunotherapy Response in Gastric Cancer |
title_full_unstemmed | A Novel Ferroptosis-Related Gene Risk Signature for Predicting Prognosis and Immunotherapy Response in Gastric Cancer |
title_short | A Novel Ferroptosis-Related Gene Risk Signature for Predicting Prognosis and Immunotherapy Response in Gastric Cancer |
title_sort | novel ferroptosis-related gene risk signature for predicting prognosis and immunotherapy response in gastric cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8642032/ https://www.ncbi.nlm.nih.gov/pubmed/34868391 http://dx.doi.org/10.1155/2021/2385406 |
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