Multi-targeted olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage

Abstract Background The complexity of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) may require the simultaneous analysis of variant types of protein biomarkers to describe it more accurately. In this study, we analyzed for the first time the alterations of cerebros...

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Main Authors: Rui Ding, Liquan Wu, Shanshan Wei, Haoran Lu, Xiaohong Qin, Xizhi Liu, Yanhua Wang, Wen Liu, Huibing Li, Baochang Luo, Teng Xie, Zhibiao Chen
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Proteome Science
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Online Access:https://doi.org/10.1186/s12953-024-00236-x
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author Rui Ding
Liquan Wu
Shanshan Wei
Haoran Lu
Xiaohong Qin
Xizhi Liu
Yanhua Wang
Wen Liu
Huibing Li
Baochang Luo
Teng Xie
Zhibiao Chen
author_facet Rui Ding
Liquan Wu
Shanshan Wei
Haoran Lu
Xiaohong Qin
Xizhi Liu
Yanhua Wang
Wen Liu
Huibing Li
Baochang Luo
Teng Xie
Zhibiao Chen
author_sort Rui Ding
collection DOAJ
description Abstract Background The complexity of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) may require the simultaneous analysis of variant types of protein biomarkers to describe it more accurately. In this study, we analyzed for the first time the alterations of cerebrospinal fluid (CSF) proteins in patients with aSAH by multi-targeted Olink proteomics, aiming to reveal the pathophysiology of DCI and provide insights into the diagnosis and treatment of aSAH. Methods Six aSAH patients and six control patients were selected, and CSF samples were analyzed by Olink Proteomics (including 96-neurology panel and 96-inflammation panel) based on Proximity Extension Assay (PEA). Differentially expressed proteins (DEPs) were acquired and bioinformatics analysis was performed. Results PCA analysis revealed better intra- and inter-group reproducibility of CSF samples in the control and aSAH groups. 23 neurology-related and 31 inflammation-relevant differential proteins were identified. In the neurology panel, compared to controls, the up-regulated proteins in the CSF of SAH patients predominantly included macrophage scavenger receptor 1 (MSR1), siglec-1, siglec-9, cathepsin C (CTSC), cathepsin S (CTSS), etc. Meanwhile, in the inflammation group, the incremental proteins mainly contained interleukin-6 (IL-6), MCP-1, CXCL10, CXCL-9, TRAIL, etc. Cluster analysis exhibited significant differences in differential proteins between the two groups. GO function enrichment analysis hinted that the differential proteins pertinent to neurology in the CSF of SAH patients were mainly involved in the regulation of defense response, vesicle-mediated transport and regulation of immune response; while the differential proteins related to inflammation were largely connected with the cellular response to chemokine, response to chemokine and chemokine-mediated signaling pathway. Additionally, in the neurology panel, KEGG enrichment analysis indicated that the differential proteins were significantly enriched in the phagosome, apoptosis and microRNAs in cancer pathway. And in the inflammation panel, the differential proteins were mainly enriched in the chemokine signaling pathway, viral protein interaction with cytokine and cytokine receptor and toll-like receptor signaling pathway. Conclusions These identified differential proteins reveal unique pathophysiological characteristics secondary to aSAH. Further characterization of these proteins and aberrant pathways in future research could enable their application as potential therapeutic targets and biomarkers for DCI after aSAH.
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spelling doaj-art-7267a5e470fb4a7fa2eef2fc37be4ae52025-08-20T02:51:48ZengBMCProteome Science1477-59562024-11-0122111510.1186/s12953-024-00236-xMulti-targeted olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhageRui Ding0Liquan Wu1Shanshan Wei2Haoran Lu3Xiaohong Qin4Xizhi Liu5Yanhua Wang6Wen Liu7Huibing Li8Baochang Luo9Teng Xie10Zhibiao Chen11Department of Neurosurgery, Renmin Hospital of Wuhan UniversityDepartment of Neurosurgery, Renmin Hospital of Wuhan UniversityDepartment of Oncology, Wuchang Hospital Affiliated to Wuhan University of Science and TechnologyDepartment of Neurosurgery, Renmin Hospital of Wuhan UniversityDepartment of Neurosurgery, Renmin Hospital of Wuhan UniversityDepartment of Neurosurgery, Renmin Hospital of Wuhan UniversityDepartment of Neurosurgery, Hanchuan Renmin HospitalDepartment of Neurosurgery, Hanchuan Renmin HospitalDepartment of Neurosurgery, Hanchuan Renmin HospitalDepartment of Neurosurgery, Hanchuan Renmin HospitalDepartment of Neurosurgery, Hanchuan Renmin HospitalDepartment of Neurosurgery, Renmin Hospital of Wuhan UniversityAbstract Background The complexity of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) may require the simultaneous analysis of variant types of protein biomarkers to describe it more accurately. In this study, we analyzed for the first time the alterations of cerebrospinal fluid (CSF) proteins in patients with aSAH by multi-targeted Olink proteomics, aiming to reveal the pathophysiology of DCI and provide insights into the diagnosis and treatment of aSAH. Methods Six aSAH patients and six control patients were selected, and CSF samples were analyzed by Olink Proteomics (including 96-neurology panel and 96-inflammation panel) based on Proximity Extension Assay (PEA). Differentially expressed proteins (DEPs) were acquired and bioinformatics analysis was performed. Results PCA analysis revealed better intra- and inter-group reproducibility of CSF samples in the control and aSAH groups. 23 neurology-related and 31 inflammation-relevant differential proteins were identified. In the neurology panel, compared to controls, the up-regulated proteins in the CSF of SAH patients predominantly included macrophage scavenger receptor 1 (MSR1), siglec-1, siglec-9, cathepsin C (CTSC), cathepsin S (CTSS), etc. Meanwhile, in the inflammation group, the incremental proteins mainly contained interleukin-6 (IL-6), MCP-1, CXCL10, CXCL-9, TRAIL, etc. Cluster analysis exhibited significant differences in differential proteins between the two groups. GO function enrichment analysis hinted that the differential proteins pertinent to neurology in the CSF of SAH patients were mainly involved in the regulation of defense response, vesicle-mediated transport and regulation of immune response; while the differential proteins related to inflammation were largely connected with the cellular response to chemokine, response to chemokine and chemokine-mediated signaling pathway. Additionally, in the neurology panel, KEGG enrichment analysis indicated that the differential proteins were significantly enriched in the phagosome, apoptosis and microRNAs in cancer pathway. And in the inflammation panel, the differential proteins were mainly enriched in the chemokine signaling pathway, viral protein interaction with cytokine and cytokine receptor and toll-like receptor signaling pathway. Conclusions These identified differential proteins reveal unique pathophysiological characteristics secondary to aSAH. Further characterization of these proteins and aberrant pathways in future research could enable their application as potential therapeutic targets and biomarkers for DCI after aSAH.https://doi.org/10.1186/s12953-024-00236-xAneurysmal subarachnoid hemorrhageOlink proteomicsNeurologyInflammationBioinformatics analysis
spellingShingle Rui Ding
Liquan Wu
Shanshan Wei
Haoran Lu
Xiaohong Qin
Xizhi Liu
Yanhua Wang
Wen Liu
Huibing Li
Baochang Luo
Teng Xie
Zhibiao Chen
Multi-targeted olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage
Proteome Science
Aneurysmal subarachnoid hemorrhage
Olink proteomics
Neurology
Inflammation
Bioinformatics analysis
title Multi-targeted olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage
title_full Multi-targeted olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage
title_fullStr Multi-targeted olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage
title_full_unstemmed Multi-targeted olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage
title_short Multi-targeted olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage
title_sort multi targeted olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage
topic Aneurysmal subarachnoid hemorrhage
Olink proteomics
Neurology
Inflammation
Bioinformatics analysis
url https://doi.org/10.1186/s12953-024-00236-x
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