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Bioinformatics analysis of the proteome in the pathway of complement and coagulation cascades in COVID-19: discovering potential biomarkers of FGB and SERPINA5

Liu et al., BMC Infectious Diseases, doi:10.1186/s12879-025-11598-8, Oct 2025
https://c19early.org/liu31.html
Bioinformatics and immunohistochemistry study identifying dysregulation in the coagulation pathway in COVID-19, highlighting FGB and FGG (upregulated) and F2 (thrombin) and SERPINA5 (downregulated) as key hub genes. The findings support using existing anticoagulants targeting F2 and suggest FGB and SERPINA5 are potential diagnostic biomarkers and therapeutic targets.
Liu et al., 8 Oct 2025, peer-reviewed, 8 authors. Contact: mitenike@sjtu.edu.cn, songshu@shaphc.org, zhanglijun@shaphc.org.
In silico studies are an important part of preclinical research, however results may be very different in vivo.
Abstract: Liu et al. BMC Infectious Diseases (2025) 25:1252 https://doi.org/10.1186/s12879-025-11598-8 BMC Infectious Diseases Open Access RESEARCH Bioinformatics analysis of the proteome in the pathway of complement and coagulation cascades in COVID-19: discovering potential biomarkers of FGB and SERPINA5 Siyuan Liu1†, Huichun Shi3†, Yuexiang Yang2†, Cuisong Zhu2, Jing Zhou2, Wenzhong Jin1*, Shu Song2* and Lijun zhang2* Abstract The complement system, a key innate immunity component, is implicated in COVID-19 pathogenesis. Proteomic studies reveal dysregulated complement and coagulation cascades (CCC) proteins in COVID-19, yet comprehensive analyses remain limited. This bioinformatics study analyzed proteomic data (from inception to January 13, 2025) across Web of Science, PubMed, EMBASE, and Wiley Online Library using keywords “complement and coagulation cascades”, “COVID-19”, and “proteomics”. Included studies compared differentially expressed proteins (DEPs) in COVID-19 patients versus healthy controls. Two reviewers independently extracted data. DEPs were analyzed via R (v4.4.2), Stata (v14), and STRING (v12.0). Twenty studies identified 3,018 DEPs, including 58 CCC-related genes (e.g., FGB, SERPINA5, FGG, F2). Hub genes were identified using MCODE and cytohubba in Cytoscape, and 16 hub genes (e.g., FGB, SERPINA5) were found. Stata confirmed consistent expression of FGB, SERPINA5, FGG, and F2. All of them are the biomarkers of diseases, and are the drug targets except SERPINA5 according to the reports from OpenTargets database. Immunohistochemistry validated FGB upregulation and SERPINA5 downregulation. In summary, CCC pathway proteins are extensively dysregulated in COVID-19. FGB and SERPINA5 are potential diagnostic biomarkers and therapeutic targets, offering insights into severe COVID-19 mechanisms and guiding novel treatment strategies. Keywords COVID-19, Proteomics, Complement and coagulation cascades, FGB, SERPINA5 † Siyuan Liu, Huichun Shi and Yuexiang Yang are contributed equally to this work. *Correspondence: Wenzhong Jin mitenike@sjtu.edu.cn Shu Song songshu@shaphc.org Lijun zhang zhanglijun@shaphc.org 1 Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, China 2 Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China 3 Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit..
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