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Ferroptosis-related gene SLC1A5 is a novel prognostic biomarker and correlates with immune infiltrates in stomach adenocarcinoma

BACKGROUND: Stomach adenocarcinoma (STAD) is associated with high morbidity and mortality rates. Ferroptosis is an iron-dependent form of cell death, which plays an important role in the development of many cancers. Tumor-associated competing endogenous RNAs (ceRNAs) regulate tumorigenesis and devel...

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Autores principales: Zhu, Dandan, Wu, Sifan, Li, Yafang, Zhang, Yu, Chen, Jierong, Ma, Jianhong, Cao, Lixue, Lyu, Zejian, Hou, Tieying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933927/
https://www.ncbi.nlm.nih.gov/pubmed/35305616
http://dx.doi.org/10.1186/s12935-022-02544-8
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author Zhu, Dandan
Wu, Sifan
Li, Yafang
Zhang, Yu
Chen, Jierong
Ma, Jianhong
Cao, Lixue
Lyu, Zejian
Hou, Tieying
author_facet Zhu, Dandan
Wu, Sifan
Li, Yafang
Zhang, Yu
Chen, Jierong
Ma, Jianhong
Cao, Lixue
Lyu, Zejian
Hou, Tieying
author_sort Zhu, Dandan
collection PubMed
description BACKGROUND: Stomach adenocarcinoma (STAD) is associated with high morbidity and mortality rates. Ferroptosis is an iron-dependent form of cell death, which plays an important role in the development of many cancers. Tumor-associated competing endogenous RNAs (ceRNAs) regulate tumorigenesis and development. Our study aimed to construct ceRNA networks and explore the relationship between ferroptosis-related genes in the ceRNA network and immune infiltration in STAD. METHODS: Based on the interactions among long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs), a ceRNA network was constructed to illustrate the relationships among lncRNAs, miRNAs, and mRNAs. Subsequently, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment analyses were carried out to explore the functions and interactions of the differentially expressed (DE) mRNAs related to the ceRNA network. Differential expression and prognostic analysis of ferroptosis-related genes in the ceRNA network were performed using the R package “limma” and “survminer.” The correlation between ferroptosis-related genes and tumor-infiltrating immune cells was analyzed using Spearman correlation analysis and CIBERSORT. Quantitative real-time PCR (qRT-PCR) was used to validate the expression of ferroptosis-related genes in STAD cells lines. RESULTS: A ceRNA network consisting of 29 DElncRNAs, 31 DEmiRNAs, and 182 DEmRNAs was constructed. These DEmRNAs were significantly enriched in pathways related to the occurrence and development of STAD. The ferroptosis-related gene SLC1A5 was upregulated in STAD (P < 0.001) and was associated with better prognosis (P = 0.049). The CIBERSORT database and Spearman correlation analysis indicated that SLC1A5 was correlated with eight types of tumor-infiltrating immune cells and immune checkpoints, including PD-L1(CD-274) and PD-1(PDCD1). The SLC1A5 mRNA was found to be highly expressed in STAD cells lines. CONCLUSIONS: Our study provides insights into the function of ceRNAs in STAD and identifies biomarkers for the development of therapies for STAD. The ferroptosis-related gene SLC1A5 in the ceRNA network was associated with both tumor-infiltrating immune cells and immune checkpoints in the tumor microenvironment, suggesting that SLC1A5 may be a novel prognostic marker and a potential target for STAD immunotherapy in the future. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02544-8.
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spelling pubmed-89339272022-03-23 Ferroptosis-related gene SLC1A5 is a novel prognostic biomarker and correlates with immune infiltrates in stomach adenocarcinoma Zhu, Dandan Wu, Sifan Li, Yafang Zhang, Yu Chen, Jierong Ma, Jianhong Cao, Lixue Lyu, Zejian Hou, Tieying Cancer Cell Int Research BACKGROUND: Stomach adenocarcinoma (STAD) is associated with high morbidity and mortality rates. Ferroptosis is an iron-dependent form of cell death, which plays an important role in the development of many cancers. Tumor-associated competing endogenous RNAs (ceRNAs) regulate tumorigenesis and development. Our study aimed to construct ceRNA networks and explore the relationship between ferroptosis-related genes in the ceRNA network and immune infiltration in STAD. METHODS: Based on the interactions among long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs), a ceRNA network was constructed to illustrate the relationships among lncRNAs, miRNAs, and mRNAs. Subsequently, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) functional enrichment analyses were carried out to explore the functions and interactions of the differentially expressed (DE) mRNAs related to the ceRNA network. Differential expression and prognostic analysis of ferroptosis-related genes in the ceRNA network were performed using the R package “limma” and “survminer.” The correlation between ferroptosis-related genes and tumor-infiltrating immune cells was analyzed using Spearman correlation analysis and CIBERSORT. Quantitative real-time PCR (qRT-PCR) was used to validate the expression of ferroptosis-related genes in STAD cells lines. RESULTS: A ceRNA network consisting of 29 DElncRNAs, 31 DEmiRNAs, and 182 DEmRNAs was constructed. These DEmRNAs were significantly enriched in pathways related to the occurrence and development of STAD. The ferroptosis-related gene SLC1A5 was upregulated in STAD (P < 0.001) and was associated with better prognosis (P = 0.049). The CIBERSORT database and Spearman correlation analysis indicated that SLC1A5 was correlated with eight types of tumor-infiltrating immune cells and immune checkpoints, including PD-L1(CD-274) and PD-1(PDCD1). The SLC1A5 mRNA was found to be highly expressed in STAD cells lines. CONCLUSIONS: Our study provides insights into the function of ceRNAs in STAD and identifies biomarkers for the development of therapies for STAD. The ferroptosis-related gene SLC1A5 in the ceRNA network was associated with both tumor-infiltrating immune cells and immune checkpoints in the tumor microenvironment, suggesting that SLC1A5 may be a novel prognostic marker and a potential target for STAD immunotherapy in the future. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12935-022-02544-8. BioMed Central 2022-03-19 /pmc/articles/PMC8933927/ /pubmed/35305616 http://dx.doi.org/10.1186/s12935-022-02544-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhu, Dandan
Wu, Sifan
Li, Yafang
Zhang, Yu
Chen, Jierong
Ma, Jianhong
Cao, Lixue
Lyu, Zejian
Hou, Tieying
Ferroptosis-related gene SLC1A5 is a novel prognostic biomarker and correlates with immune infiltrates in stomach adenocarcinoma
title Ferroptosis-related gene SLC1A5 is a novel prognostic biomarker and correlates with immune infiltrates in stomach adenocarcinoma
title_full Ferroptosis-related gene SLC1A5 is a novel prognostic biomarker and correlates with immune infiltrates in stomach adenocarcinoma
title_fullStr Ferroptosis-related gene SLC1A5 is a novel prognostic biomarker and correlates with immune infiltrates in stomach adenocarcinoma
title_full_unstemmed Ferroptosis-related gene SLC1A5 is a novel prognostic biomarker and correlates with immune infiltrates in stomach adenocarcinoma
title_short Ferroptosis-related gene SLC1A5 is a novel prognostic biomarker and correlates with immune infiltrates in stomach adenocarcinoma
title_sort ferroptosis-related gene slc1a5 is a novel prognostic biomarker and correlates with immune infiltrates in stomach adenocarcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933927/
https://www.ncbi.nlm.nih.gov/pubmed/35305616
http://dx.doi.org/10.1186/s12935-022-02544-8
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