Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion

BACKGROUND: Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is a devastating cerebrovascular disorder, which could benefit from collateral circulation. Proteins associated with acute LVO pathogenesis and endothelial function may appear in blood samples of AIS patients due to LVO, thu...

Descripción completa

Detalles Bibliográficos
Autores principales: Qin, Chuan, Zhao, Xin-Ling, Ma, Xiao-Tong, Zhou, Luo-Qi, Wu, Long-jun, Shang, Ke, Wang, Wei, Tian, Dai-Shi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604304/
https://www.ncbi.nlm.nih.gov/pubmed/31262327
http://dx.doi.org/10.1186/s12967-019-1962-8
_version_ 1783431683538681856
author Qin, Chuan
Zhao, Xin-Ling
Ma, Xiao-Tong
Zhou, Luo-Qi
Wu, Long-jun
Shang, Ke
Wang, Wei
Tian, Dai-Shi
author_facet Qin, Chuan
Zhao, Xin-Ling
Ma, Xiao-Tong
Zhou, Luo-Qi
Wu, Long-jun
Shang, Ke
Wang, Wei
Tian, Dai-Shi
author_sort Qin, Chuan
collection PubMed
description BACKGROUND: Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is a devastating cerebrovascular disorder, which could benefit from collateral circulation. Proteins associated with acute LVO pathogenesis and endothelial function may appear in blood samples of AIS patients due to LVO, thus permitting development of blood-based biomarkers for its diagnosis and prognosis. METHODS: This study is a single-center, retrospective, observational case–control trial. Consecutive patients who presented at the Department of Neurology of Tongji Hospital were recruited from July 2016 to April 2018. In the discovery phase, a proteomic approach with iTRAQ-based LC–MS/MS was used to investigate the altered proteomic pattern in plasma from patients with AIS due to LVO. In the validation study, Western blots was used to identify biomarkers associated with stroke diagnosis as well as their prognostic value associated with different collateral statuses. RESULTS: For this exploratory study, the proteomic analysis of plasma from 40 patients with AIS due to LVO and 20 healthy controls revealed seven differentially expressed proteins with a 1.2/0.83-fold or greater difference between groups. The four elevated proteins, PPBP (1.58 ± 0.78 vs 0.98 ± 0.37; P < 0.001), THBS1 (1.13 ± 0.88 vs 0.43 ± 0.26; P < 0.001), LYVE1 (1.61 ± 0.55 vs 0.97 ± 0.50; P < 0.001), and IGF2 (1.19 ± 0.42 vs 0.86 ± 0.24; P < 0.001), were verified by Western blots analysis in an independent cohort including 33 patients and 33 controls. A strong interaction was observed between the four-protein panel and the diagnosis of AIS due to LVO (AUC 0.947; P < 0.001). Furthermore, IGF2, LYVE1, and THBS1 were closely associated with collateral status (IGF2 0.115, 95% CI 0.016–0.841, P = 0.033; LYVE1 0.183, 95% CI 0.036–0.918, P = 0.039; THBS1 4.257, 95% CI 1.273–14.228, P = 0.019), and proved to be independent predictors of good outcome (IGF2 0.115, 95% CI 0.015–0.866, P = 0.036; LYVE1 0.028, 95% CI 0.002–0.334, P = 0.005; THBS1 3.294, 95% CI 1.158–9.372, P = 0.025) at a 3-month follow-up. CONCLUSIONS: The identified 4-biomarker panel could provide diagnostic aid to the existing imaging modalities for AIS due to LVO, and the prognostic value of IGF2, LYVE1, and THBS1 was proved in predicting functional outcomes related to collateral status. Trial registration ClinicalTrials.gov NCT 03122002. Retrospectively registered April 20, 2017. URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/NCT03122002?term=NCT+03122002&rank=1 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-019-1962-8) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-6604304
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-66043042019-07-12 Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion Qin, Chuan Zhao, Xin-Ling Ma, Xiao-Tong Zhou, Luo-Qi Wu, Long-jun Shang, Ke Wang, Wei Tian, Dai-Shi J Transl Med Research BACKGROUND: Acute ischemic stroke (AIS) due to large vessel occlusion (LVO) is a devastating cerebrovascular disorder, which could benefit from collateral circulation. Proteins associated with acute LVO pathogenesis and endothelial function may appear in blood samples of AIS patients due to LVO, thus permitting development of blood-based biomarkers for its diagnosis and prognosis. METHODS: This study is a single-center, retrospective, observational case–control trial. Consecutive patients who presented at the Department of Neurology of Tongji Hospital were recruited from July 2016 to April 2018. In the discovery phase, a proteomic approach with iTRAQ-based LC–MS/MS was used to investigate the altered proteomic pattern in plasma from patients with AIS due to LVO. In the validation study, Western blots was used to identify biomarkers associated with stroke diagnosis as well as their prognostic value associated with different collateral statuses. RESULTS: For this exploratory study, the proteomic analysis of plasma from 40 patients with AIS due to LVO and 20 healthy controls revealed seven differentially expressed proteins with a 1.2/0.83-fold or greater difference between groups. The four elevated proteins, PPBP (1.58 ± 0.78 vs 0.98 ± 0.37; P < 0.001), THBS1 (1.13 ± 0.88 vs 0.43 ± 0.26; P < 0.001), LYVE1 (1.61 ± 0.55 vs 0.97 ± 0.50; P < 0.001), and IGF2 (1.19 ± 0.42 vs 0.86 ± 0.24; P < 0.001), were verified by Western blots analysis in an independent cohort including 33 patients and 33 controls. A strong interaction was observed between the four-protein panel and the diagnosis of AIS due to LVO (AUC 0.947; P < 0.001). Furthermore, IGF2, LYVE1, and THBS1 were closely associated with collateral status (IGF2 0.115, 95% CI 0.016–0.841, P = 0.033; LYVE1 0.183, 95% CI 0.036–0.918, P = 0.039; THBS1 4.257, 95% CI 1.273–14.228, P = 0.019), and proved to be independent predictors of good outcome (IGF2 0.115, 95% CI 0.015–0.866, P = 0.036; LYVE1 0.028, 95% CI 0.002–0.334, P = 0.005; THBS1 3.294, 95% CI 1.158–9.372, P = 0.025) at a 3-month follow-up. CONCLUSIONS: The identified 4-biomarker panel could provide diagnostic aid to the existing imaging modalities for AIS due to LVO, and the prognostic value of IGF2, LYVE1, and THBS1 was proved in predicting functional outcomes related to collateral status. Trial registration ClinicalTrials.gov NCT 03122002. Retrospectively registered April 20, 2017. URL of trial registry record: https://www.clinicaltrials.gov/ct2/show/NCT03122002?term=NCT+03122002&rank=1 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-019-1962-8) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-01 /pmc/articles/PMC6604304/ /pubmed/31262327 http://dx.doi.org/10.1186/s12967-019-1962-8 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Qin, Chuan
Zhao, Xin-Ling
Ma, Xiao-Tong
Zhou, Luo-Qi
Wu, Long-jun
Shang, Ke
Wang, Wei
Tian, Dai-Shi
Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion
title Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion
title_full Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion
title_fullStr Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion
title_full_unstemmed Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion
title_short Proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion
title_sort proteomic profiling of plasma biomarkers in acute ischemic stroke due to large vessel occlusion
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604304/
https://www.ncbi.nlm.nih.gov/pubmed/31262327
http://dx.doi.org/10.1186/s12967-019-1962-8
work_keys_str_mv AT qinchuan proteomicprofilingofplasmabiomarkersinacuteischemicstrokeduetolargevesselocclusion
AT zhaoxinling proteomicprofilingofplasmabiomarkersinacuteischemicstrokeduetolargevesselocclusion
AT maxiaotong proteomicprofilingofplasmabiomarkersinacuteischemicstrokeduetolargevesselocclusion
AT zhouluoqi proteomicprofilingofplasmabiomarkersinacuteischemicstrokeduetolargevesselocclusion
AT wulongjun proteomicprofilingofplasmabiomarkersinacuteischemicstrokeduetolargevesselocclusion
AT shangke proteomicprofilingofplasmabiomarkersinacuteischemicstrokeduetolargevesselocclusion
AT wangwei proteomicprofilingofplasmabiomarkersinacuteischemicstrokeduetolargevesselocclusion
AT tiandaishi proteomicprofilingofplasmabiomarkersinacuteischemicstrokeduetolargevesselocclusion