Bioinformatics analysis of ferroptosis-related genes and immune cell infiltration in non-alcoholic fatty liver disease

Abstract Background The morbidity and mortality rates of patients with non-alcoholic fatty liver disease (NAFLD) have been steadily increasing in recent years. Previous studies have confirmed the important role of ferroptosis in NAFLD development; however, the precise mechanism through which ferropt...

Full description

Bibliographic Details
Main Authors: Huan Zhang, Malina Axinbai, Yuqing Zhao, Jiaoyang Wei, Tongshuo Qu, Jingmin Kong, Yongqiang He, Liping Zhang
Format: Article
Language:English
Published: BMC 2023-12-01
Series:European Journal of Medical Research
Subjects:
Online Access:https://doi.org/10.1186/s40001-023-01457-0
_version_ 1797377172273364992
author Huan Zhang
Malina Axinbai
Yuqing Zhao
Jiaoyang Wei
Tongshuo Qu
Jingmin Kong
Yongqiang He
Liping Zhang
author_facet Huan Zhang
Malina Axinbai
Yuqing Zhao
Jiaoyang Wei
Tongshuo Qu
Jingmin Kong
Yongqiang He
Liping Zhang
author_sort Huan Zhang
collection DOAJ
description Abstract Background The morbidity and mortality rates of patients with non-alcoholic fatty liver disease (NAFLD) have been steadily increasing in recent years. Previous studies have confirmed the important role of ferroptosis in NAFLD development; however, the precise mechanism through which ferroptosis influences NAFLD occurrence remains unclear. The present study aimed to identify and validate ferroptosis-related genes involved in NAFLD pathogenesis and to investigate the underlying molecular mechanisms of NAFLD. Methods We downloaded microarray datasets GSE72756 and GSE24807 to identify differentially expressed genes (DEGs) between samples from healthy individuals and patients with NAFLD. From these DEGs, we extracted ferroptosis-related DEGs. GSE89632, another microarray dataset, was used to validate the expression of ferroptosis-related genes. A protein–protein interaction (PPI) network of ferroptosis-related genes was then constructed. The target genes were also subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, competing endogenous RNA networks were constructed. We used the CIBERSORT package to evaluate the infiltration of immune cells infiltration in NAFLD. Results Five ferroptosis-related genes (SCP2, MUC1, DPP4, SLC1A4, and TF) were identified as promising diagnostic biomarkers for NAFLD. Enrichment analyses revealed that these genes are mainly involved in metabolic processes. NEAT1-miR-1224-5p-SCP2, NEAT1-miR-485-5p-MUC1, MALAT1-miR-485-5p-MUC1, and CNOT6-miR-145-5p-SLC1A4 are likely to be the potential RNA regulatory pathways that affect NAFLD development. Principal component analysis indicated significant differences in immune cell infiltration between the two groups. Conclusions This study identified five ferroptosis-related genes as potential biomarkers for diagnosing NAFLD. The correlations between the expression of ferroptosis-related genes and immune cell infiltration might shed light on the study of the molecular mechanism underlying NAFLD development.
first_indexed 2024-03-08T19:48:54Z
format Article
id doaj.art-fe06e9228ea143cebf6b928910ac187f
institution Directory Open Access Journal
issn 2047-783X
language English
last_indexed 2024-03-08T19:48:54Z
publishDate 2023-12-01
publisher BMC
record_format Article
series European Journal of Medical Research
spelling doaj.art-fe06e9228ea143cebf6b928910ac187f2023-12-24T12:12:53ZengBMCEuropean Journal of Medical Research2047-783X2023-12-0128111410.1186/s40001-023-01457-0Bioinformatics analysis of ferroptosis-related genes and immune cell infiltration in non-alcoholic fatty liver diseaseHuan Zhang0Malina Axinbai1Yuqing Zhao2Jiaoyang Wei3Tongshuo Qu4Jingmin Kong5Yongqiang He6Liping Zhang7Department of Digestion, Dongfang Hospital, Beijing University of Chinese MedicineDepartment of Digestion, Dongfang Hospital, Beijing University of Chinese MedicineBeijing University of Chinese MedicineDepartment of Digestion, Dongfang Hospital, Beijing University of Chinese MedicineDepartment of Digestion, Dongfang Hospital, Beijing University of Chinese MedicineDepartment of Emergency, Beijing Chaoyang Integrative Medicine Rescue and First Aid HospitalDepartment of Digestion, Dongzhimen Hospital, Beijing University of Chinese MedicineDepartment of Digestion, Dongfang Hospital, Beijing University of Chinese MedicineAbstract Background The morbidity and mortality rates of patients with non-alcoholic fatty liver disease (NAFLD) have been steadily increasing in recent years. Previous studies have confirmed the important role of ferroptosis in NAFLD development; however, the precise mechanism through which ferroptosis influences NAFLD occurrence remains unclear. The present study aimed to identify and validate ferroptosis-related genes involved in NAFLD pathogenesis and to investigate the underlying molecular mechanisms of NAFLD. Methods We downloaded microarray datasets GSE72756 and GSE24807 to identify differentially expressed genes (DEGs) between samples from healthy individuals and patients with NAFLD. From these DEGs, we extracted ferroptosis-related DEGs. GSE89632, another microarray dataset, was used to validate the expression of ferroptosis-related genes. A protein–protein interaction (PPI) network of ferroptosis-related genes was then constructed. The target genes were also subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, competing endogenous RNA networks were constructed. We used the CIBERSORT package to evaluate the infiltration of immune cells infiltration in NAFLD. Results Five ferroptosis-related genes (SCP2, MUC1, DPP4, SLC1A4, and TF) were identified as promising diagnostic biomarkers for NAFLD. Enrichment analyses revealed that these genes are mainly involved in metabolic processes. NEAT1-miR-1224-5p-SCP2, NEAT1-miR-485-5p-MUC1, MALAT1-miR-485-5p-MUC1, and CNOT6-miR-145-5p-SLC1A4 are likely to be the potential RNA regulatory pathways that affect NAFLD development. Principal component analysis indicated significant differences in immune cell infiltration between the two groups. Conclusions This study identified five ferroptosis-related genes as potential biomarkers for diagnosing NAFLD. The correlations between the expression of ferroptosis-related genes and immune cell infiltration might shed light on the study of the molecular mechanism underlying NAFLD development.https://doi.org/10.1186/s40001-023-01457-0Non-alcoholic fatty liver diseaseNAFLDFerroptosisBioinformatics analysisImmune
spellingShingle Huan Zhang
Malina Axinbai
Yuqing Zhao
Jiaoyang Wei
Tongshuo Qu
Jingmin Kong
Yongqiang He
Liping Zhang
Bioinformatics analysis of ferroptosis-related genes and immune cell infiltration in non-alcoholic fatty liver disease
European Journal of Medical Research
Non-alcoholic fatty liver disease
NAFLD
Ferroptosis
Bioinformatics analysis
Immune
title Bioinformatics analysis of ferroptosis-related genes and immune cell infiltration in non-alcoholic fatty liver disease
title_full Bioinformatics analysis of ferroptosis-related genes and immune cell infiltration in non-alcoholic fatty liver disease
title_fullStr Bioinformatics analysis of ferroptosis-related genes and immune cell infiltration in non-alcoholic fatty liver disease
title_full_unstemmed Bioinformatics analysis of ferroptosis-related genes and immune cell infiltration in non-alcoholic fatty liver disease
title_short Bioinformatics analysis of ferroptosis-related genes and immune cell infiltration in non-alcoholic fatty liver disease
title_sort bioinformatics analysis of ferroptosis related genes and immune cell infiltration in non alcoholic fatty liver disease
topic Non-alcoholic fatty liver disease
NAFLD
Ferroptosis
Bioinformatics analysis
Immune
url https://doi.org/10.1186/s40001-023-01457-0
work_keys_str_mv AT huanzhang bioinformaticsanalysisofferroptosisrelatedgenesandimmunecellinfiltrationinnonalcoholicfattyliverdisease
AT malinaaxinbai bioinformaticsanalysisofferroptosisrelatedgenesandimmunecellinfiltrationinnonalcoholicfattyliverdisease
AT yuqingzhao bioinformaticsanalysisofferroptosisrelatedgenesandimmunecellinfiltrationinnonalcoholicfattyliverdisease
AT jiaoyangwei bioinformaticsanalysisofferroptosisrelatedgenesandimmunecellinfiltrationinnonalcoholicfattyliverdisease
AT tongshuoqu bioinformaticsanalysisofferroptosisrelatedgenesandimmunecellinfiltrationinnonalcoholicfattyliverdisease
AT jingminkong bioinformaticsanalysisofferroptosisrelatedgenesandimmunecellinfiltrationinnonalcoholicfattyliverdisease
AT yongqianghe bioinformaticsanalysisofferroptosisrelatedgenesandimmunecellinfiltrationinnonalcoholicfattyliverdisease
AT lipingzhang bioinformaticsanalysisofferroptosisrelatedgenesandimmunecellinfiltrationinnonalcoholicfattyliverdisease