Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
General Research Article

FYN and CD247: Key Genes for Septic Shock Based on Bioinformatics and Meta-Analysis

Author(s): Yue Jiang, Qian Miao, Lin Hu, Tingyan Zhou, Yingchun Hu* and Ye Tian*

Volume 25, Issue 10, 2022

Published on: 14 January, 2022

Page: [1722 - 1730] Pages: 9

DOI: 10.2174/1386207324666210816123508

Price: $65

Abstract

Background: Septic shock is sepsis accompanied by hemodynamic instability and high clinical mortality.

Materials and Methods: GSE95233, GSE57065, GSE131761 gene-expression profiles of healthy control subjects and septic shock patients were downloaded from the Gene-Expression Omnibus (GEO) database, and differences of expression profiles and their intersection were analysed using GEO2R. Function and pathway enrichment analysis was performed on common differentially expressed genes (DEG), and key genes for septic shock were screened using a protein-protein interaction network created with STRING. Also, data from the GEO database were used for survival analysis for key genes, and a meta-analysis was used to explore expression trends of core genes. Finally, high-throughput sequencing using the blood of a murine sepsis model was performed to analyse the expression of CD247 and FYN in mice.

Results: A total of 539 DEGs were obtained (p < 0.05). Gene ontology analysis showed that key genes were enriched in functions, such as immune response and T cell activity, and DEGs were enriched in signal pathways, such as T cell receptors. FYN and CD247 are in the centre of the protein-protein interaction network, and survival analysis found that they are positively correlated with survival from sepsis. Further, meta-analysis results showed that FYN could be useful for the prognosis of patients, and CD247 might distinguish between sepsis and systemic inflammatory response syndrome patients. Finally, RNA sequencing using a mouse septic shock model showed low expression of CD247 and FYN in this model.

Conclusion: FYN and CD247 are expected to become new biomarkers of septic shock.

Keywords: Septic shock, FYN, CD247, bioinformatics, prognosis, differential diagnosis.

« Previous Next »
Graphical Abstract

[1]
Orkin, S.H.; Reilly, P. MEDICINE. Paying for future success in gene therapy. Science, 2016, 352(6289), 1059-1061.
[http://dx.doi.org/10.1126/science.aaf4770] [PMID: 27230368]
[2]
Sevransky, J.E.; Nour, S.; Susla, G.M.; Needham, D.M.; Hollenberg, S.; Pronovost, P. Hemodynamic goals in randomized clinical trials in patients with sepsis: a systematic review of the literature. Crit. Care, 2007, 11(3), R67.
[http://dx.doi.org/10.1186/cc5948] [PMID: 17584921]
[3]
Naegeli, A.; Bratanis, E.; Karlsson, C.; Shannon, O.; Kalluru, R.; Linder, A.; Malmström, J.; Collin, M. Streptococcus pyogenes evades adaptive immunity through specific IgG glycan hydrolysis. J. Exp. Med., 2019, 216(7), 1615-1629.
[http://dx.doi.org/10.1084/jem.20190293] [PMID: 31092533]
[4]
Liu, Z.; Triba, M.N.; Amathieu, R.; Lin, X.; Bouchemal, N.; Hantz, E.; Le Moyec, L.; Savarin, P. Nuclear magnetic resonance-based serum metabolomic analysis reveals different disease evolution profiles between septic shock survivors and non-survivors. Crit. Care, 2019, 23(1), 169.
[http://dx.doi.org/10.1186/s13054-019-2456-z] [PMID: 31088568]
[5]
Shankar-Hari, M.; Phillips, G.S.; Levy, M.L.; Seymour, C.W.; Liu, V.X.; Deutschman, C.S.; Angus, D.C.; Rubenfeld, G.D.; Singer, M. Developing a new definition and assessing new clinical criteria for septic shock: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 2016, 315(8), 775-787.
[http://dx.doi.org/10.1001/jama.2016.0289] [PMID: 26903336]
[6]
Thille, A.W.; Mauri, T.; Talmor, D. Update in critical care medicine 2017. Am. J. Respir. Crit. Care Med., 2018, 197(11), 1382-1388.
[http://dx.doi.org/10.1164/rccm.201801-0055UP] [PMID: 29554433]
[7]
Dünser, M.W.; Russell, J.A. Getting down to the real question: effects of transfusion triggers on long-term survival and quality of life following septic shock; Springer, 2016.
[8]
Rhee, C.; Kadri, S.S.; Danner, R.L.; Suffredini, A.F.; Massaro, A.F.; Kitch, B.T.; Lee, G.; Klompas, M. Diagnosing sepsis is subjective and highly variable: a survey of intensivists using case vignettes. Crit. Care, 2016, 20(1), 89.
[http://dx.doi.org/10.1186/s13054-016-1266-9] [PMID: 27048508]
[9]
Tabone, O.; Mommert, M.; Jourdan, C.; Cerrato, E.; Legrand, M.; Lepape, A.; Allaouchiche, B.; Rimmelé, T.; Pachot, A.; Monneret, G.; Venet, F.; Mallet, F.; Textoris, J. Endogenous retroviruses transcriptional modulation after severe infection, trauma and burn. Front. Immunol., 2019, 9, 3091.
[http://dx.doi.org/10.3389/fimmu.2018.03091] [PMID: 30671061]
[10]
Barrett, T.; Wilhite, S.E.; Ledoux, P.; Evangelista, C.; Kim, I.F.; Tomashevsky, M.; Marshall, K.A.; Phillippy, K.H.; Sherman, P.M.; Holko, M.; Yefanov, A.; Lee, H.; Zhang, N.; Robertson, C.L.; Serova, N.; Davis, S.; Soboleva, A. NCBI GEO: archive for functional genomics data sets-update. Nucleic Acids Res., 2013, 41(Database issue), D991-D995.
[PMID: 23193258]
[11]
Van, P.; Jiang, W.; Gottardo, R.; Finak, G. ggCyto: next generation open-source visualization software for cytometry. Bioinformatics, 2018, 34(22), 3951-3953.
[http://dx.doi.org/10.1093/bioinformatics/bty441] [PMID: 29868771]
[12]
Yu, G.; Wang, L-G.; Han, Y.; He, Q-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS, 2012, 16(5), 284-287.
[http://dx.doi.org/10.1089/omi.2011.0118] [PMID: 22455463]
[13]
von Mering, C.; Huynen, M.; Jaeggi, D.; Schmidt, S.; Bork, P.; Snel, B. STRING: a database of predicted functional associations between proteins. Nucleic Acids Res., 2003, 31(1), 258-261.
[http://dx.doi.org/10.1093/nar/gkg034] [PMID: 12519996]
[14]
Parnell, G.P.; Tang, B.M.; Nalos, M.; Armstrong, N.J.; Huang, S.J.; Booth, D.R.; McLean, A.S. Identifying key regulatory genes in the whole blood of septic patients to monitor underlying immune dysfunctions. Shock, 2013, 40(3), 166-174.
[http://dx.doi.org/10.1097/SHK.0b013e31829ee604] [PMID: 23807251]
[15]
Tsalik, E.L.; Langley, R.J.; Dinwiddie, D.L.; Miller, N.A.; Yoo, B.; van Velkinburgh, J.C.; Smith, L.D.; Thiffault, I.; Jaehne, A.K.; Valente, A.M.; Henao, R.; Yuan, X.; Glickman, S.W.; Rice, B.J.; McClain, M.T.; Carin, L.; Corey, G.R.; Ginsburg, G.S.; Cairns, C.B.; Otero, R.M.; Fowler, V.G., Jr; Rivers, E.P.; Woods, C.W.; Kingsmore, S.F. An integrated transcriptome and expressed variant analysis of sepsis survival and death. Genome Med., 2014, 6(11), 111.
[http://dx.doi.org/10.1186/s13073-014-0111-5] [PMID: 25538794]
[16]
Tang, B.M.; McLean, A.S.; Dawes, I.W.; Huang, S.J.; Cowley, M.J.; Lin, R.C. Gene-expression profiling of gram-positive and gram-negative sepsis in critically ill patients. Crit. Care Med., 2008, 36(4), 1125-1128.
[http://dx.doi.org/10.1097/CCM.0b013e3181692c0b] [PMID: 18379237]
[17]
Maslove, D.M.; Tang, B.M.; McLean, A.S. Identification of sepsis subtypes in critically ill adults using gene expression profiling. Crit. Care, 2012, 16(5), R183.
[http://dx.doi.org/10.1186/cc11667] [PMID: 23036193]
[18]
Sutherland, A.; Thomas, M.; Brandon, R.A.; Brandon, R.B.; Lipman, J.; Tang, B.; McLean, A.; Pascoe, R.; Price, G.; Nguyen, T.; Stone, G.; Venter, D. Development and validation of a novel molecular biomarker diagnostic test for the early detection of sepsis. Crit. Care, 2011, 15(3), R149.
[http://dx.doi.org/10.1186/cc10274] [PMID: 21682927]
[19]
McHugh, L.; Seldon, T.A.; Brandon, R.A.; Kirk, J.T.; Rapisarda, A.; Sutherland, A.J.; Presneill, J.J.; Venter, D.J.; Lipman, J.; Thomas, M.R.; Klein Klouwenberg, P.M.; van Vught, L.; Scicluna, B.; Bonten, M.; Cremer, O.L.; Schultz, M.J.; van der Poll, T.; Yager, T.D.; Brandon, R.B. A molecular host response assay to discriminate between sepsis and infection-negative systemic inflammation in critically ill patients: discovery and validation in independent cohorts. PLoS Med., 2015, 12(12), e1001916.
[http://dx.doi.org/10.1371/journal.pmed.1001916] [PMID: 26645559]
[20]
Chen, M.; Chen, X.; Hu, Y.; Cai, X. Screening of key genes related to the prognosis of mouse sepsis. Biosci. Rep., 2020, 40(10), BSR20202649.
[http://dx.doi.org/10.1042/BSR20202649] [PMID: 33015708]
[21]
Kim, J.S.; Kim, Y-J.; Ryoo, S.M.; Sohn, C.H.; Seo, D.W.; Ahn, S.; Lim, K.S.; Kim, W.Y. One-year progression and risk factors for the development of chronic kidney disease in septic shock patients with acute kidney injury: a single-centre retrospective cohort study. J. Clin. Med., 2018, 7(12), 554.
[http://dx.doi.org/10.3390/jcm7120554] [PMID: 30558341]
[22]
Lewis, J.M.; Feasey, N.A.; Rylance, J. Aetiology and outcomes of sepsis in adults in sub-Saharan Africa: a systematic review and meta-analysis. Crit. Care, 2019, 23(1), 212.
[http://dx.doi.org/10.1186/s13054-019-2501-y] [PMID: 31186062]
[23]
Zador, Z.; Landry, A.; Cusimano, M.D.; Geifman, N. Multimorbidity states associated with higher mortality rates in organ dysfunction and sepsis: a data-driven analysis in critical care. Crit. Care, 2019, 23(1), 247.
[http://dx.doi.org/10.1186/s13054-019-2486-6] [PMID: 31287020]
[24]
Lundholm, M.; Mayans, S.; Motta, V.; Löfgren-Burström, A.; Danska, J.; Holmberg, D. Variation in the Cd3 ζ (Cd247) gene correlates with altered T cell activation and is associated with autoimmune diabetes. J. Immunol., 2010, 184(10), 5537-5544.
[http://dx.doi.org/10.4049/jimmunol.0904012] [PMID: 20400699]
[25]
Pang, M.; Setoyama, Y.; Tsuzaka, K.; Yoshimoto, K.; Amano, K.; Abe, T.; Takeuchi, T. Defective expression and tyrosine phosphorylation of the T cell receptor zeta chain in peripheral blood T cells from systemic lupus erythematosus patients. Clin. Exp. Immunol., 2002, 129(1), 160-168.
[http://dx.doi.org/10.1046/j.1365-2249.2002.01833.x] [PMID: 12100036]
[26]
Ban, K.; Gao, Y.; Amin, H.M.; Howard, A.; Miller, C.; Lin, Q.; Leng, X.; Munsell, M.; Bar-Eli, M.; Arlinghaus, R.B.; Chandra, J. BCR-ABL1 mediates up-regulation of Fyn in chronic myelogenous leukemia. Blood, 2008, 111(5), 2904-2908.
[http://dx.doi.org/10.1182/blood-2007-05-091769] [PMID: 18180382]
[27]
Zhang, X.; Mei, D.; Zhang, L.; Wei, W. Src Family Protein Kinase Controls the Fate of B Cells in Autoimmune Diseases. Inflammation, 2020, 1-11.
[PMID: 33037966]
[28]
Kozlowska, A.; Hrycaj, P.; Lacki, J.K.; Jagodzinski, P.P. Fyn and CD70 expression in CD4+ T cells from patients with systemic lupus erythematosus. J. Rheumatol., 2010, 37(1), 53-59.
[http://dx.doi.org/10.3899/jrheum.090424] [PMID: 19955046]
[29]
Choudhry, M.A.; Uddin, S.; Sayeed, M.M. Prostaglandin E2 modulation of p59fyn tyrosine kinase in T lymphocytes during sepsis. J. Immunol., 1998, 160(2), 929-935.
[PMID: 9551931]

Rights & Permissions Print Cite
Article Metrics
36
1
© 2024 Bentham Science Publishers | Privacy Policy