Plasma proteomics-based biomarkers for predicting response to mesenchymal stem cell therapy in severe COVID-19

Abstract Background The objective of this study was to identify potential biomarkers for predicting response to MSC therapy by pre-MSC treatment plasma proteomic profile in severe COVID-19 in order to optimize treatment choice. Methods A total of 58 patients selected from our previous RCT cohort wer...

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Main Authors: Tian-Tian Li, Wei-Qi Yao, Hai-Bo Dong, Ze-Rui Wang, Zi-Ying Zhang, Meng-Qi Yuan, Lei Shi, Fu-Sheng Wang
Format: Article
Language:English
Published: BMC 2023-12-01
Series:Stem Cell Research & Therapy
Subjects:
Online Access:https://doi.org/10.1186/s13287-023-03573-4
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author Tian-Tian Li
Wei-Qi Yao
Hai-Bo Dong
Ze-Rui Wang
Zi-Ying Zhang
Meng-Qi Yuan
Lei Shi
Fu-Sheng Wang
author_facet Tian-Tian Li
Wei-Qi Yao
Hai-Bo Dong
Ze-Rui Wang
Zi-Ying Zhang
Meng-Qi Yuan
Lei Shi
Fu-Sheng Wang
author_sort Tian-Tian Li
collection DOAJ
description Abstract Background The objective of this study was to identify potential biomarkers for predicting response to MSC therapy by pre-MSC treatment plasma proteomic profile in severe COVID-19 in order to optimize treatment choice. Methods A total of 58 patients selected from our previous RCT cohort were enrolled in this study. MSC responders (n = 35) were defined as whose resolution of lung consolidation ≥ 51.99% (the median value for resolution of lung consolidation) from pre-MSC to 28 days post-MSC treatment, while non-responders (n = 23) were defined as whose resolution of lung consolidation < 51.99%. Plasma before MSC treatment was detected using data-independent acquisition (DIA) proteomics. Multivariate logistic regression analysis was used to identify pre-MSC treatment plasma proteomic biomarkers that might distinguish between responders and non-responders to MSC therapy. Results In total, 1101 proteins were identified in plasma. Compared with the non-responders, the responders had three upregulated proteins (CSPG2, CTRB1, and OSCAR) and 10 downregulated proteins (ANXA1, AGRG6, CAPG, DDX55, KV133, LEG10, OXSR1, PICAL, PTGDS, and S100A8) in plasma before MSC treatment. Using logistic regression model, lower levels of DDX55, AGRG6, PICAL, and ANXA1 and higher levels of CTRB1 pre-MSC treatment were predictors of responders to MSC therapy, with AUC of the ROC at 0.910 (95% CI 0.818–1.000) in the training set. In the validation set, AUC of the ROC was 0.767 (95% CI 0.459–1.000). Conclusions The responsiveness to MSC therapy appears to depend on baseline level of DDX55, AGRG6, PICAL, CTRB1, and ANXA1. Clinicians should take these factors into consideration when making decision to initiate MSC therapy in patients with severe COVID-19.
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spelling doaj.art-a74c9b25ca614aa7b23375336555ea902023-12-17T12:08:43ZengBMCStem Cell Research & Therapy1757-65122023-12-0114111110.1186/s13287-023-03573-4Plasma proteomics-based biomarkers for predicting response to mesenchymal stem cell therapy in severe COVID-19Tian-Tian Li0Wei-Qi Yao1Hai-Bo Dong2Ze-Rui Wang3Zi-Ying Zhang4Meng-Qi Yuan5Lei Shi6Fu-Sheng Wang7Senior Department of Infectious Diseases, The Fifth Medical Centre of PLA General Hospital, National Clinical Research Center for Infectious DiseasesDepartment of Biology and Medicine, Hubei University of TechnologyWuhan Optics Valley Vcanbio Cell & Gene Technology Co., Ltd.Department of Gastroenterology, First Medical Center of Chinese, PLA General HospitalSenior Department of Infectious Diseases, The Fifth Medical Centre of PLA General Hospital, National Clinical Research Center for Infectious DiseasesSenior Department of Infectious Diseases, The Fifth Medical Centre of PLA General Hospital, National Clinical Research Center for Infectious DiseasesSenior Department of Infectious Diseases, The Fifth Medical Centre of PLA General Hospital, National Clinical Research Center for Infectious DiseasesSenior Department of Infectious Diseases, The Fifth Medical Centre of PLA General Hospital, National Clinical Research Center for Infectious DiseasesAbstract Background The objective of this study was to identify potential biomarkers for predicting response to MSC therapy by pre-MSC treatment plasma proteomic profile in severe COVID-19 in order to optimize treatment choice. Methods A total of 58 patients selected from our previous RCT cohort were enrolled in this study. MSC responders (n = 35) were defined as whose resolution of lung consolidation ≥ 51.99% (the median value for resolution of lung consolidation) from pre-MSC to 28 days post-MSC treatment, while non-responders (n = 23) were defined as whose resolution of lung consolidation < 51.99%. Plasma before MSC treatment was detected using data-independent acquisition (DIA) proteomics. Multivariate logistic regression analysis was used to identify pre-MSC treatment plasma proteomic biomarkers that might distinguish between responders and non-responders to MSC therapy. Results In total, 1101 proteins were identified in plasma. Compared with the non-responders, the responders had three upregulated proteins (CSPG2, CTRB1, and OSCAR) and 10 downregulated proteins (ANXA1, AGRG6, CAPG, DDX55, KV133, LEG10, OXSR1, PICAL, PTGDS, and S100A8) in plasma before MSC treatment. Using logistic regression model, lower levels of DDX55, AGRG6, PICAL, and ANXA1 and higher levels of CTRB1 pre-MSC treatment were predictors of responders to MSC therapy, with AUC of the ROC at 0.910 (95% CI 0.818–1.000) in the training set. In the validation set, AUC of the ROC was 0.767 (95% CI 0.459–1.000). Conclusions The responsiveness to MSC therapy appears to depend on baseline level of DDX55, AGRG6, PICAL, CTRB1, and ANXA1. Clinicians should take these factors into consideration when making decision to initiate MSC therapy in patients with severe COVID-19.https://doi.org/10.1186/s13287-023-03573-4COVID-19Mesenchymal stem cellsProteomicsPredictive model
spellingShingle Tian-Tian Li
Wei-Qi Yao
Hai-Bo Dong
Ze-Rui Wang
Zi-Ying Zhang
Meng-Qi Yuan
Lei Shi
Fu-Sheng Wang
Plasma proteomics-based biomarkers for predicting response to mesenchymal stem cell therapy in severe COVID-19
Stem Cell Research & Therapy
COVID-19
Mesenchymal stem cells
Proteomics
Predictive model
title Plasma proteomics-based biomarkers for predicting response to mesenchymal stem cell therapy in severe COVID-19
title_full Plasma proteomics-based biomarkers for predicting response to mesenchymal stem cell therapy in severe COVID-19
title_fullStr Plasma proteomics-based biomarkers for predicting response to mesenchymal stem cell therapy in severe COVID-19
title_full_unstemmed Plasma proteomics-based biomarkers for predicting response to mesenchymal stem cell therapy in severe COVID-19
title_short Plasma proteomics-based biomarkers for predicting response to mesenchymal stem cell therapy in severe COVID-19
title_sort plasma proteomics based biomarkers for predicting response to mesenchymal stem cell therapy in severe covid 19
topic COVID-19
Mesenchymal stem cells
Proteomics
Predictive model
url https://doi.org/10.1186/s13287-023-03573-4
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