Cargando…
Role of ferroptosis-associated genes in ankylosing spondylitis and immune cell infiltration
Ankylosing spondylitis (AS) is a chronic progressive autoimmune disease with insidious onset, high rates of disability among patients, unknown pathogenesis, and no effective treatment. Ferroptosis is a novel type of regulated cell death that is associated with various cancers and diseases. However,...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691995/ https://www.ncbi.nlm.nih.gov/pubmed/36437923 http://dx.doi.org/10.3389/fgene.2022.948290 |
_version_ | 1784837159148060672 |
---|---|
author | Li, Qiaochu Chen, Zhiyu Yang, Chaohua Wang, Linbang Ma, Jingjin He, Tao Li, Huanhuan Quan, Zhengxue |
author_facet | Li, Qiaochu Chen, Zhiyu Yang, Chaohua Wang, Linbang Ma, Jingjin He, Tao Li, Huanhuan Quan, Zhengxue |
author_sort | Li, Qiaochu |
collection | PubMed |
description | Ankylosing spondylitis (AS) is a chronic progressive autoimmune disease with insidious onset, high rates of disability among patients, unknown pathogenesis, and no effective treatment. Ferroptosis is a novel type of regulated cell death that is associated with various cancers and diseases. However, its relation to AS is not clear. In the present study, we identified two potential therapeutic targets for AS based on genes associated with ferroptosis and explored their association with immune cells and immune cell infiltration (ICI). We studied gene expression profiles of two cohorts of patients with AS (GSE25101 and GSE41038) derived from the gene expression omnibus database, and ferroptosis-associated genes (FRGs) were obtained from the FerrDb database. LASSO regression analysis was performed to build predictive models for AS based on FRGs, and the ferroptosis level in each sample was assessed via single-sample gene set enrichment analysis. Weighted gene co-expression network and protein-protein interaction network analyses were performed for screening; two key genes, DDIT3 and HSPB1, were identified in patients with AS. The relationship between key genes and ICI levels was assessed using the CIBERSORT algorithm, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, DDIT3 and HSPB1 were identified as diagnostic markers and potential therapeutic targets for AS. DDIT3 was highly positively correlated with the infiltration levels of various immune cells, while HSPB1 was negatively correlated with the infiltration levels of several different types of immune cells. In conclusion, DDIT3 and HSPB1 may induce ferroptosis in the cells of patients with AS via changes in the inflammatory response in the immune microenvironment, and these genes could serve as molecular targets for AS therapy. |
format | Online Article Text |
id | pubmed-9691995 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96919952022-11-26 Role of ferroptosis-associated genes in ankylosing spondylitis and immune cell infiltration Li, Qiaochu Chen, Zhiyu Yang, Chaohua Wang, Linbang Ma, Jingjin He, Tao Li, Huanhuan Quan, Zhengxue Front Genet Genetics Ankylosing spondylitis (AS) is a chronic progressive autoimmune disease with insidious onset, high rates of disability among patients, unknown pathogenesis, and no effective treatment. Ferroptosis is a novel type of regulated cell death that is associated with various cancers and diseases. However, its relation to AS is not clear. In the present study, we identified two potential therapeutic targets for AS based on genes associated with ferroptosis and explored their association with immune cells and immune cell infiltration (ICI). We studied gene expression profiles of two cohorts of patients with AS (GSE25101 and GSE41038) derived from the gene expression omnibus database, and ferroptosis-associated genes (FRGs) were obtained from the FerrDb database. LASSO regression analysis was performed to build predictive models for AS based on FRGs, and the ferroptosis level in each sample was assessed via single-sample gene set enrichment analysis. Weighted gene co-expression network and protein-protein interaction network analyses were performed for screening; two key genes, DDIT3 and HSPB1, were identified in patients with AS. The relationship between key genes and ICI levels was assessed using the CIBERSORT algorithm, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, DDIT3 and HSPB1 were identified as diagnostic markers and potential therapeutic targets for AS. DDIT3 was highly positively correlated with the infiltration levels of various immune cells, while HSPB1 was negatively correlated with the infiltration levels of several different types of immune cells. In conclusion, DDIT3 and HSPB1 may induce ferroptosis in the cells of patients with AS via changes in the inflammatory response in the immune microenvironment, and these genes could serve as molecular targets for AS therapy. Frontiers Media S.A. 2022-11-11 /pmc/articles/PMC9691995/ /pubmed/36437923 http://dx.doi.org/10.3389/fgene.2022.948290 Text en Copyright © 2022 Li, Chen, Yang, Wang, Ma, He, Li and Quan. 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 | Genetics Li, Qiaochu Chen, Zhiyu Yang, Chaohua Wang, Linbang Ma, Jingjin He, Tao Li, Huanhuan Quan, Zhengxue Role of ferroptosis-associated genes in ankylosing spondylitis and immune cell infiltration |
title | Role of ferroptosis-associated genes in ankylosing spondylitis and immune cell infiltration |
title_full | Role of ferroptosis-associated genes in ankylosing spondylitis and immune cell infiltration |
title_fullStr | Role of ferroptosis-associated genes in ankylosing spondylitis and immune cell infiltration |
title_full_unstemmed | Role of ferroptosis-associated genes in ankylosing spondylitis and immune cell infiltration |
title_short | Role of ferroptosis-associated genes in ankylosing spondylitis and immune cell infiltration |
title_sort | role of ferroptosis-associated genes in ankylosing spondylitis and immune cell infiltration |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9691995/ https://www.ncbi.nlm.nih.gov/pubmed/36437923 http://dx.doi.org/10.3389/fgene.2022.948290 |
work_keys_str_mv | AT liqiaochu roleofferroptosisassociatedgenesinankylosingspondylitisandimmunecellinfiltration AT chenzhiyu roleofferroptosisassociatedgenesinankylosingspondylitisandimmunecellinfiltration AT yangchaohua roleofferroptosisassociatedgenesinankylosingspondylitisandimmunecellinfiltration AT wanglinbang roleofferroptosisassociatedgenesinankylosingspondylitisandimmunecellinfiltration AT majingjin roleofferroptosisassociatedgenesinankylosingspondylitisandimmunecellinfiltration AT hetao roleofferroptosisassociatedgenesinankylosingspondylitisandimmunecellinfiltration AT lihuanhuan roleofferroptosisassociatedgenesinankylosingspondylitisandimmunecellinfiltration AT quanzhengxue roleofferroptosisassociatedgenesinankylosingspondylitisandimmunecellinfiltration |