Metabolomic characterization benefits the identification of acute lung injury in patients with type A acute aortic dissection

Introduction: Acute aortic dissection (AAD) often leads to the development of acute lung injury (ALI). However, the early detection and diagnosis of AAD in patients with ALI pose significant challenges. The objective of this study is to investigate distinct metabolic alterations in the plasma sample...

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Main Authors: Linglin Fan, Ke Meng, Fanqi Meng, Yuan Wu, Ling Lin
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-08-01
Series:Frontiers in Molecular Biosciences
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fmolb.2023.1222133/full
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author Linglin Fan
Ke Meng
Fanqi Meng
Yuan Wu
Yuan Wu
Ling Lin
author_facet Linglin Fan
Ke Meng
Fanqi Meng
Yuan Wu
Yuan Wu
Ling Lin
author_sort Linglin Fan
collection DOAJ
description Introduction: Acute aortic dissection (AAD) often leads to the development of acute lung injury (ALI). However, the early detection and diagnosis of AAD in patients with ALI pose significant challenges. The objective of this study is to investigate distinct metabolic alterations in the plasma samples of AAD patients with ALI, AAD patients without ALI, and healthy individuals.Method: Between September 2019 and September 2022, we retrospectively collected data from 228 AAD patients who were diagnosed with ALI through post-surgery chest X-ray and PaO2/FiO2 assessments. Univariate analysis was employed to identify pre-surgery risk factors for ALI. Additionally, we conducted high-throughput target metabolic analysis on 90 plasma samples, comprising 30 samples from AAD patients with ALI, 30 from patients with AAD only, and 30 from healthy controls. After LC-MS spectral processing and metabolite quantification, the recursive feature elimination with cross-validation (RFECV) analysis based on the random forest was used to select the optimal metabolites as a diagnostic panel for the detection of AAD patients with ALI. The support vector machines (SVM) machine learning model was further applied to validate the diagnostic accuracy of the established biomarker panel.Results: In the univariate analysis, preoperative β-HB and TNF-α exhibited a significant association with lung injury (OR = 0.906, 95% CI 0.852–0.965, p = 0.002; OR = 1.007, 95% CI 1.003–1.011, p < 0.0001). The multiple-reaction monitoring analysis of 417 common metabolites identified significant changes in 145 metabolites (fold change >1.2 or <0.833, p < 0.05) across the three groups. Multivariate statistical analysis revealed notable differences between AAD patients and healthy controls. When compared with the non-ALI group, AAD patients with ALI displayed remarkable upregulation in 19 metabolites and downregulation in 4 metabolites. Particularly, combining citric acid and glucuronic acid as a biomarker panel improved the classification performance for distinguishing between the ALI and non-ALI groups.Discussion: Differentially expressed metabolites in the ALI group were primarily involved in amino acids biosynthesis, carbohydrate metabolism (TCA cycle), arginine and proline metabolism, and glucagon signaling pathway. These findings demonstrate a great potential of the targeted metabolomic approach for screening, routine surveillance, and diagnosis of pulmonary injury in patients with AAD.
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spelling doaj.art-c1d18d07c81b44e5bb998e08721a5b082023-08-03T12:01:02ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-08-011010.3389/fmolb.2023.12221331222133Metabolomic characterization benefits the identification of acute lung injury in patients with type A acute aortic dissectionLinglin Fan0Ke Meng1Fanqi Meng2Yuan Wu3Yuan Wu4Ling Lin5Xiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, ChinaMedical College, Guangxi University, Nanning, Guangxi, ChinaXiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, ChinaXiamen Cardiovascular Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, ChinaDepartment of Cardiac Surgery, Yue Bei People’s Hospital, Shaoguan, Guangdong, ChinaShanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, ChinaIntroduction: Acute aortic dissection (AAD) often leads to the development of acute lung injury (ALI). However, the early detection and diagnosis of AAD in patients with ALI pose significant challenges. The objective of this study is to investigate distinct metabolic alterations in the plasma samples of AAD patients with ALI, AAD patients without ALI, and healthy individuals.Method: Between September 2019 and September 2022, we retrospectively collected data from 228 AAD patients who were diagnosed with ALI through post-surgery chest X-ray and PaO2/FiO2 assessments. Univariate analysis was employed to identify pre-surgery risk factors for ALI. Additionally, we conducted high-throughput target metabolic analysis on 90 plasma samples, comprising 30 samples from AAD patients with ALI, 30 from patients with AAD only, and 30 from healthy controls. After LC-MS spectral processing and metabolite quantification, the recursive feature elimination with cross-validation (RFECV) analysis based on the random forest was used to select the optimal metabolites as a diagnostic panel for the detection of AAD patients with ALI. The support vector machines (SVM) machine learning model was further applied to validate the diagnostic accuracy of the established biomarker panel.Results: In the univariate analysis, preoperative β-HB and TNF-α exhibited a significant association with lung injury (OR = 0.906, 95% CI 0.852–0.965, p = 0.002; OR = 1.007, 95% CI 1.003–1.011, p < 0.0001). The multiple-reaction monitoring analysis of 417 common metabolites identified significant changes in 145 metabolites (fold change >1.2 or <0.833, p < 0.05) across the three groups. Multivariate statistical analysis revealed notable differences between AAD patients and healthy controls. When compared with the non-ALI group, AAD patients with ALI displayed remarkable upregulation in 19 metabolites and downregulation in 4 metabolites. Particularly, combining citric acid and glucuronic acid as a biomarker panel improved the classification performance for distinguishing between the ALI and non-ALI groups.Discussion: Differentially expressed metabolites in the ALI group were primarily involved in amino acids biosynthesis, carbohydrate metabolism (TCA cycle), arginine and proline metabolism, and glucagon signaling pathway. These findings demonstrate a great potential of the targeted metabolomic approach for screening, routine surveillance, and diagnosis of pulmonary injury in patients with AAD.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1222133/fullacute lung injuryacute aortic dissectiontargeted metabolomicsdiagnostic panelpathway enrichment analysis
spellingShingle Linglin Fan
Ke Meng
Fanqi Meng
Yuan Wu
Yuan Wu
Ling Lin
Metabolomic characterization benefits the identification of acute lung injury in patients with type A acute aortic dissection
Frontiers in Molecular Biosciences
acute lung injury
acute aortic dissection
targeted metabolomics
diagnostic panel
pathway enrichment analysis
title Metabolomic characterization benefits the identification of acute lung injury in patients with type A acute aortic dissection
title_full Metabolomic characterization benefits the identification of acute lung injury in patients with type A acute aortic dissection
title_fullStr Metabolomic characterization benefits the identification of acute lung injury in patients with type A acute aortic dissection
title_full_unstemmed Metabolomic characterization benefits the identification of acute lung injury in patients with type A acute aortic dissection
title_short Metabolomic characterization benefits the identification of acute lung injury in patients with type A acute aortic dissection
title_sort metabolomic characterization benefits the identification of acute lung injury in patients with type a acute aortic dissection
topic acute lung injury
acute aortic dissection
targeted metabolomics
diagnostic panel
pathway enrichment analysis
url https://www.frontiersin.org/articles/10.3389/fmolb.2023.1222133/full
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