Identification of ferroptosis related biomarkers and immune infiltration in Parkinson’s disease by integrated bioinformatic analysis

Abstract Background Increasing evidence has indicated that ferroptosis engages in the progression of Parkinson’s disease (PD). This study aimed to explore the role of ferroptosis-related genes (FRGs), immune infiltration and immune checkpoint genes (ICGs) in the pathogenesis and development of PD. M...

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Main Authors: Na Xing, Ziye Dong, Qiaoli Wu, Yufeng Zhang, Pengcheng Kan, Yuan Han, Xiuli Cheng, Yaru Wang, Biao Zhang
Format: Article
Language:English
Published: BMC 2023-03-01
Series:BMC Medical Genomics
Subjects:
Online Access:https://doi.org/10.1186/s12920-023-01481-3
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author Na Xing
Ziye Dong
Qiaoli Wu
Yufeng Zhang
Pengcheng Kan
Yuan Han
Xiuli Cheng
Yaru Wang
Biao Zhang
author_facet Na Xing
Ziye Dong
Qiaoli Wu
Yufeng Zhang
Pengcheng Kan
Yuan Han
Xiuli Cheng
Yaru Wang
Biao Zhang
author_sort Na Xing
collection DOAJ
description Abstract Background Increasing evidence has indicated that ferroptosis engages in the progression of Parkinson’s disease (PD). This study aimed to explore the role of ferroptosis-related genes (FRGs), immune infiltration and immune checkpoint genes (ICGs) in the pathogenesis and development of PD. Methods The microarray data of PD patients and healthy controls (HC) from the Gene Expression Omnibus (GEO) database was downloaded. Weighted gene co-expression network analysis (WGCNA) was processed to identify the significant modules related to PD in the GSE18838 dataset. Machine learning algorithms were used to screen the candidate biomarkers based on the intersect between WGCNA, FRGs and differentially expressed genes. Enrichment analysis of GSVA, GSEA, GO, KEGG, and immune infiltration, group comparison of ICGs were also performed. Next, candidate biomarkers were validated in clinical samples by ELISA and receiver operating characteristic curve (ROC) was used to assess diagnose ability. Results In this study, FRGs had correlations with ICGs, immune infiltration. Then, plasma levels of LPIN1 in PD was significantly lower than that in healthy controls, while the expression of TNFAIP3 was higher in PD in comparison with HC. ROC curves showed that the area under curve (AUC) of the LPIN1 and TNFAIP3 combination was 0.833 (95% CI: 0.750–0.916). Moreover, each biomarker alone could discriminate the PD from HC (LPIN1: AUC = 0.754, 95% CI: 0.659–0.849; TNFAIP3: AUC = 0.754, 95% CI: 0.660–0.849). For detection of early PD from HC, the model of combination maintained diagnostic accuracy with an AUC of 0.831 (95% CI: 0.734–0.927), LPIN1 also performed well in distinguishing the early PD from HC (AUC = 0.817, 95% CI: 0.717–0.917). However, the diagnostic efficacy was relatively poor in distinguishing the early from middle-advanced PD patients. Conclusion The combination model composed of LPIN1 and TNFAIP3, and each biomarker may serve as an efficient tool for distinguishing PD from HC.
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spelling doaj.art-4a7389e3564a4308b3d73f0401b46efe2023-03-22T12:37:57ZengBMCBMC Medical Genomics1755-87942023-03-0116111710.1186/s12920-023-01481-3Identification of ferroptosis related biomarkers and immune infiltration in Parkinson’s disease by integrated bioinformatic analysisNa Xing0Ziye Dong1Qiaoli Wu2Yufeng Zhang3Pengcheng Kan4Yuan Han5Xiuli Cheng6Yaru Wang7Biao Zhang8Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical UniversityClinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical UniversityTianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Tianjin Huanhu HospitalClinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical UniversityDepartment of Clinical Laboratory, Tianjin Huanhu HospitalDepartment of Clinical Laboratory, Tianjin Huanhu HospitalDepartment of Clinical Laboratory, Tianjin Huanhu HospitalChu Hsien-I Memorial Hospital (Metabolic Diseases Hospital) of Tianjin Medical UniversityClinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical UniversityAbstract Background Increasing evidence has indicated that ferroptosis engages in the progression of Parkinson’s disease (PD). This study aimed to explore the role of ferroptosis-related genes (FRGs), immune infiltration and immune checkpoint genes (ICGs) in the pathogenesis and development of PD. Methods The microarray data of PD patients and healthy controls (HC) from the Gene Expression Omnibus (GEO) database was downloaded. Weighted gene co-expression network analysis (WGCNA) was processed to identify the significant modules related to PD in the GSE18838 dataset. Machine learning algorithms were used to screen the candidate biomarkers based on the intersect between WGCNA, FRGs and differentially expressed genes. Enrichment analysis of GSVA, GSEA, GO, KEGG, and immune infiltration, group comparison of ICGs were also performed. Next, candidate biomarkers were validated in clinical samples by ELISA and receiver operating characteristic curve (ROC) was used to assess diagnose ability. Results In this study, FRGs had correlations with ICGs, immune infiltration. Then, plasma levels of LPIN1 in PD was significantly lower than that in healthy controls, while the expression of TNFAIP3 was higher in PD in comparison with HC. ROC curves showed that the area under curve (AUC) of the LPIN1 and TNFAIP3 combination was 0.833 (95% CI: 0.750–0.916). Moreover, each biomarker alone could discriminate the PD from HC (LPIN1: AUC = 0.754, 95% CI: 0.659–0.849; TNFAIP3: AUC = 0.754, 95% CI: 0.660–0.849). For detection of early PD from HC, the model of combination maintained diagnostic accuracy with an AUC of 0.831 (95% CI: 0.734–0.927), LPIN1 also performed well in distinguishing the early PD from HC (AUC = 0.817, 95% CI: 0.717–0.917). However, the diagnostic efficacy was relatively poor in distinguishing the early from middle-advanced PD patients. Conclusion The combination model composed of LPIN1 and TNFAIP3, and each biomarker may serve as an efficient tool for distinguishing PD from HC.https://doi.org/10.1186/s12920-023-01481-3Parkinson’s diseaseFerroptosisImmune infiltrationImmune checkpoint geneELISABioinformatic
spellingShingle Na Xing
Ziye Dong
Qiaoli Wu
Yufeng Zhang
Pengcheng Kan
Yuan Han
Xiuli Cheng
Yaru Wang
Biao Zhang
Identification of ferroptosis related biomarkers and immune infiltration in Parkinson’s disease by integrated bioinformatic analysis
BMC Medical Genomics
Parkinson’s disease
Ferroptosis
Immune infiltration
Immune checkpoint gene
ELISA
Bioinformatic
title Identification of ferroptosis related biomarkers and immune infiltration in Parkinson’s disease by integrated bioinformatic analysis
title_full Identification of ferroptosis related biomarkers and immune infiltration in Parkinson’s disease by integrated bioinformatic analysis
title_fullStr Identification of ferroptosis related biomarkers and immune infiltration in Parkinson’s disease by integrated bioinformatic analysis
title_full_unstemmed Identification of ferroptosis related biomarkers and immune infiltration in Parkinson’s disease by integrated bioinformatic analysis
title_short Identification of ferroptosis related biomarkers and immune infiltration in Parkinson’s disease by integrated bioinformatic analysis
title_sort identification of ferroptosis related biomarkers and immune infiltration in parkinson s disease by integrated bioinformatic analysis
topic Parkinson’s disease
Ferroptosis
Immune infiltration
Immune checkpoint gene
ELISA
Bioinformatic
url https://doi.org/10.1186/s12920-023-01481-3
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