Proteomic analysis of plasma and duodenal tissue in celiac disease patients reveals potential noninvasive diagnostic biomarkers

Abstract The pathogenesis of celiac disease (CeD) remains incompletely understood. Traditional diagnostic techniques for CeD include serological testing and endoscopic examination; however, they have limitations. Therefore, there is a need to identify novel noninvasive biomarkers for CeD diagnosis....

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Main Authors: Na Li, Ayinuer Maimaitireyimu, Tian Shi, Yan Feng, Weidong Liu, Shenglong Xue, Feng Gao
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-80391-5
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author Na Li
Ayinuer Maimaitireyimu
Tian Shi
Yan Feng
Weidong Liu
Shenglong Xue
Feng Gao
author_facet Na Li
Ayinuer Maimaitireyimu
Tian Shi
Yan Feng
Weidong Liu
Shenglong Xue
Feng Gao
author_sort Na Li
collection DOAJ
description Abstract The pathogenesis of celiac disease (CeD) remains incompletely understood. Traditional diagnostic techniques for CeD include serological testing and endoscopic examination; however, they have limitations. Therefore, there is a need to identify novel noninvasive biomarkers for CeD diagnosis. We analyzed duodenal and plasma samples from CeD patients by four-dimensional data-dependent acquisition (4D-DIA) proteomics. Differentially expressed proteins (DEPs) were identified for functional analysis and to propose blood biomarkers associated with CeD diagnosis. In duodenal and plasma samples, respectively, 897 and 140 DEPs were identified. Combining weighted gene co-expression network analysis(WGCNA) with the DEPs, five key proteins were identified across three machine learning methods. FGL2 and TXNDC5 were significantly elevated in the CeD group, while CHGA expression showed an increasing trend, but without statistical significance. The receiver operating characteristic curve results indicated an area under the curve (AUC) of 0.7711 for FGL2 and 0.6978 for TXNDC5, with a combined AUC of 0.8944. Exploratory analysis using Mfuzz and three machine learning methods identified four plasma proteins potentially associated with CeD pathological grading (Marsh classification): FABP, CPOX, BHMT, and PPP2CB. We conclude that FGL2 and TXNDC5 deserve exploration as potential sensitive, noninvasive diagnostic biomarkers for CeD.
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spelling doaj-art-c7c9c3a83c2b4b6180b849a6859b86ce2024-12-08T12:26:59ZengNature PortfolioScientific Reports2045-23222024-12-0114111210.1038/s41598-024-80391-5Proteomic analysis of plasma and duodenal tissue in celiac disease patients reveals potential noninvasive diagnostic biomarkersNa Li0Ayinuer Maimaitireyimu1Tian Shi2Yan Feng3Weidong Liu4Shenglong Xue5Feng Gao6Xinjiang Medical University, Xinjiang Uygur Autonomous RegionDepartment of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous RegionDepartment of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous RegionDepartment of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous RegionDepartment of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous RegionCollege of Life Science and Technology, Xinjiang UniversityDepartment of Gastroenterology, People’s Hospital of Xinjiang Uygur Autonomous Region, Xinjiang Uygur Autonomous RegionAbstract The pathogenesis of celiac disease (CeD) remains incompletely understood. Traditional diagnostic techniques for CeD include serological testing and endoscopic examination; however, they have limitations. Therefore, there is a need to identify novel noninvasive biomarkers for CeD diagnosis. We analyzed duodenal and plasma samples from CeD patients by four-dimensional data-dependent acquisition (4D-DIA) proteomics. Differentially expressed proteins (DEPs) were identified for functional analysis and to propose blood biomarkers associated with CeD diagnosis. In duodenal and plasma samples, respectively, 897 and 140 DEPs were identified. Combining weighted gene co-expression network analysis(WGCNA) with the DEPs, five key proteins were identified across three machine learning methods. FGL2 and TXNDC5 were significantly elevated in the CeD group, while CHGA expression showed an increasing trend, but without statistical significance. The receiver operating characteristic curve results indicated an area under the curve (AUC) of 0.7711 for FGL2 and 0.6978 for TXNDC5, with a combined AUC of 0.8944. Exploratory analysis using Mfuzz and three machine learning methods identified four plasma proteins potentially associated with CeD pathological grading (Marsh classification): FABP, CPOX, BHMT, and PPP2CB. We conclude that FGL2 and TXNDC5 deserve exploration as potential sensitive, noninvasive diagnostic biomarkers for CeD.https://doi.org/10.1038/s41598-024-80391-5Celiac disease4D-DIA proteomicsMachine learningWGCNAMarsh classificationBiomarker
spellingShingle Na Li
Ayinuer Maimaitireyimu
Tian Shi
Yan Feng
Weidong Liu
Shenglong Xue
Feng Gao
Proteomic analysis of plasma and duodenal tissue in celiac disease patients reveals potential noninvasive diagnostic biomarkers
Scientific Reports
Celiac disease
4D-DIA proteomics
Machine learning
WGCNA
Marsh classification
Biomarker
title Proteomic analysis of plasma and duodenal tissue in celiac disease patients reveals potential noninvasive diagnostic biomarkers
title_full Proteomic analysis of plasma and duodenal tissue in celiac disease patients reveals potential noninvasive diagnostic biomarkers
title_fullStr Proteomic analysis of plasma and duodenal tissue in celiac disease patients reveals potential noninvasive diagnostic biomarkers
title_full_unstemmed Proteomic analysis of plasma and duodenal tissue in celiac disease patients reveals potential noninvasive diagnostic biomarkers
title_short Proteomic analysis of plasma and duodenal tissue in celiac disease patients reveals potential noninvasive diagnostic biomarkers
title_sort proteomic analysis of plasma and duodenal tissue in celiac disease patients reveals potential noninvasive diagnostic biomarkers
topic Celiac disease
4D-DIA proteomics
Machine learning
WGCNA
Marsh classification
Biomarker
url https://doi.org/10.1038/s41598-024-80391-5
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