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Published in: BMC Infectious Diseases 1/2024

Open Access 01-12-2024 | Septicemia | Research

Exploring the biomarkers and potential therapeutic drugs for sepsis via integrated bioinformatic analysis

Authors: Pingping Liang, Yongjian Wu, Siying Qu, Muhammad Younis, Wei Wang, Zhilong Wu, Xi Huang

Published in: BMC Infectious Diseases | Issue 1/2024

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Abstract

Background

Sepsis is a life-threatening condition caused by an excessive inflammatory response to an infection, associated with high mortality. However, the regulatory mechanism of sepsis remains unclear.

Results

In this study, bioinformatics analysis revealed the novel key biomarkers associated with sepsis and potential regulators. Three public datasets (GSE28750, GSE57065 and GSE95233) were employed to recognize the differentially expressed genes (DEGs). Taking the intersection of DEGs from these three datasets, GO and KEGG pathway enrichment analysis revealed 537 shared DEGs and their biological functions and pathways. These genes were mainly enriched in T cell activation, differentiation, lymphocyte differentiation, mononuclear cell differentiation, and regulation of T cell activation based on GO analysis. Further, pathway enrichment analysis revealed that these DEGs were significantly enriched in Th1, Th2 and Th17 cell differentiation. Additionally, five hub immune-related genes (CD3E, HLA-DRA, IL2RB, ITK and LAT) were identified from the protein–protein interaction network, and sepsis patients with higher expression of hub genes had a better prognosis. Besides, 14 drugs targeting these five hub related genes were revealed on the basis of the DrugBank database, which proved advantageous for treating immune-related diseases.

Conclusions

These results strengthen the new understanding of sepsis development and provide a fresh perspective into discriminating the candidate biomarkers for predicting sepsis as well as identifying new drugs for treating sepsis.
Appendix
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Literature
1.
go back to reference Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2018;14(2):121–37.PubMedCrossRef Venet F, Monneret G. Advances in the understanding and treatment of sepsis-induced immunosuppression. Nat Rev Nephrol. 2018;14(2):121–37.PubMedCrossRef
2.
go back to reference Deutschman CS, Tracey KJ. Sepsis: current dogma and new perspectives. Immun. 2014;40(4):463–75.CrossRef Deutschman CS, Tracey KJ. Sepsis: current dogma and new perspectives. Immun. 2014;40(4):463–75.CrossRef
4.
go back to reference Reinhart K, Daniels R, Kissoon N, Machado FR, Schachter RD, Finfer S. Recognizing sepsis as a global health priority - a who resolution. N Engl J Med. 2017;377(5):414–7.PubMedCrossRef Reinhart K, Daniels R, Kissoon N, Machado FR, Schachter RD, Finfer S. Recognizing sepsis as a global health priority - a who resolution. N Engl J Med. 2017;377(5):414–7.PubMedCrossRef
5.
go back to reference Markwart R, Saito H, Harder T, Tomczyk S, Cassini A, Fleischmann-Struzek C, et al. Epidemiology and burden of sepsis acquired in hospitals and intensive care units: a systematic review and meta-analysis. Intensive Care Med. 2020;46(8):1536–51.PubMedPubMedCentralCrossRef Markwart R, Saito H, Harder T, Tomczyk S, Cassini A, Fleischmann-Struzek C, et al. Epidemiology and burden of sepsis acquired in hospitals and intensive care units: a systematic review and meta-analysis. Intensive Care Med. 2020;46(8):1536–51.PubMedPubMedCentralCrossRef
6.
go back to reference van der Poll T, van de Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017;17(7):407–20.PubMedCrossRef van der Poll T, van de Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017;17(7):407–20.PubMedCrossRef
7.
go back to reference Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med. 1997;25(7):1095–100.PubMedCrossRef Zeni F, Freeman B, Natanson C. Anti-inflammatory therapies to treat sepsis and septic shock: a reassessment. Crit Care Med. 1997;25(7):1095–100.PubMedCrossRef
8.
go back to reference Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181–247.PubMedPubMedCentralCrossRef Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021;47(11):1181–247.PubMedPubMedCentralCrossRef
9.
go back to reference van der Poll T, Shankar-Hari M, Wiersinga WJ. The immunology of sepsis. Immun. 2021;54(11):2450–64.CrossRef van der Poll T, Shankar-Hari M, Wiersinga WJ. The immunology of sepsis. Immun. 2021;54(11):2450–64.CrossRef
10.
11.
go back to reference Bandyopadhyay S, Lysak N, Adhikari L, Velez LM, Sautina L, Mohandas R, et al. Discovery and validation of urinary molecular signature of early sepsis. Critic Care Explorat. 2020;2(10):e0195.CrossRef Bandyopadhyay S, Lysak N, Adhikari L, Velez LM, Sautina L, Mohandas R, et al. Discovery and validation of urinary molecular signature of early sepsis. Critic Care Explorat. 2020;2(10):e0195.CrossRef
12.
go back to reference Antoranz A, Sakellaropoulos T, Saez-Rodriguez J, Alexopoulos LG. Mechanism-based biomarker discovery. Drug Discov Today. 2017;22(8):1209–15.PubMedCrossRef Antoranz A, Sakellaropoulos T, Saez-Rodriguez J, Alexopoulos LG. Mechanism-based biomarker discovery. Drug Discov Today. 2017;22(8):1209–15.PubMedCrossRef
13.
go back to reference Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376(23):2235–44.PubMedPubMedCentralCrossRef Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376(23):2235–44.PubMedPubMedCentralCrossRef
14.
go back to reference Centner FS, Schoettler JJ, Fairley AM, Lindner HA, Schneider-Lindner V, Weiss C, et al. Impact of different consensus definition criteria on sepsis diagnosis in a cohort of critically ill patients-Insights from a new mathematical probabilistic approach to mortality-based validation of sepsis criteria. PLoS ONE. 2020;15(9):e0238548.PubMedPubMedCentralCrossRef Centner FS, Schoettler JJ, Fairley AM, Lindner HA, Schneider-Lindner V, Weiss C, et al. Impact of different consensus definition criteria on sepsis diagnosis in a cohort of critically ill patients-Insights from a new mathematical probabilistic approach to mortality-based validation of sepsis criteria. PLoS ONE. 2020;15(9):e0238548.PubMedPubMedCentralCrossRef
15.
go back to reference Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol. 2006;6(11):813–22.PubMedCrossRef Hotchkiss RS, Nicholson DW. Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol. 2006;6(11):813–22.PubMedCrossRef
16.
go back to reference Dey J, Mahapatra SR, Raj TK, Kaur T, Jain P, Tiwari A, et al. Designing a novel multi-epitope vaccine to evoke a robust immune response against pathogenic multidrug-resistant Enterococcus faecium bacterium. Gut Pathogens. 2022;14(1):21.PubMedPubMedCentralCrossRef Dey J, Mahapatra SR, Raj TK, Kaur T, Jain P, Tiwari A, et al. Designing a novel multi-epitope vaccine to evoke a robust immune response against pathogenic multidrug-resistant Enterococcus faecium bacterium. Gut Pathogens. 2022;14(1):21.PubMedPubMedCentralCrossRef
17.
go back to reference Dey J, Mahapatra SR, Lata S, Patro S, Misra N, Suar M. Exploring Klebsiella pneumoniae capsule polysaccharide proteins to design multiepitope subunit vaccine to fight against pneumonia. Expert Rev Vacc. 2022;21(4):569–87.CrossRef Dey J, Mahapatra SR, Lata S, Patro S, Misra N, Suar M. Exploring Klebsiella pneumoniae capsule polysaccharide proteins to design multiepitope subunit vaccine to fight against pneumonia. Expert Rev Vacc. 2022;21(4):569–87.CrossRef
18.
go back to reference Mahapatra SR, Dey J, Raj TK, Kumar V, Ghosh M, Verma KK, et al. The potential of plant-derived secondary metabolites as novel drug candidates against Klebsiella pneumoniae: Molecular docking and simulation investigation. S Afr J Bot. 2022;149:789–97.CrossRef Mahapatra SR, Dey J, Raj TK, Kumar V, Ghosh M, Verma KK, et al. The potential of plant-derived secondary metabolites as novel drug candidates against Klebsiella pneumoniae: Molecular docking and simulation investigation. S Afr J Bot. 2022;149:789–97.CrossRef
19.
go back to reference Zhang B, Zhong W, Yang B, Li Y, Duan S, Huang J, et al. Gene expression profiling reveals candidate biomarkers and probable molecular mechanisms in chronic stress. Bioengineered. 2022;13(3):6048–60.PubMedPubMedCentralCrossRef Zhang B, Zhong W, Yang B, Li Y, Duan S, Huang J, et al. Gene expression profiling reveals candidate biomarkers and probable molecular mechanisms in chronic stress. Bioengineered. 2022;13(3):6048–60.PubMedPubMedCentralCrossRef
21.
go back to reference Churko JM, Mantalas GL, Snyder MP, Wu JC. Overview of high throughput sequencing technologies to elucidate molecular pathways in cardiovascular diseases. Circ Res. 2013;112(12):1613–23.PubMedCrossRef Churko JM, Mantalas GL, Snyder MP, Wu JC. Overview of high throughput sequencing technologies to elucidate molecular pathways in cardiovascular diseases. Circ Res. 2013;112(12):1613–23.PubMedCrossRef
22.
go back to reference Jacquier A. The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs. Nat Rev Genet. 2009;10(12):833–44.PubMedCrossRef Jacquier A. The complex eukaryotic transcriptome: unexpected pervasive transcription and novel small RNAs. Nat Rev Genet. 2009;10(12):833–44.PubMedCrossRef
24.
go back to reference Popov DV, Makhnovskii PA, Shagimardanova EI, Gazizova GR, Lysenko EA, Gusev OA, et al. Contractile activity-specific transcriptome response to acute endurance exercise and training in human skeletal muscle. American J Physiolog-Endocrinol Metabol. 2019;316(4):E605–14.CrossRef Popov DV, Makhnovskii PA, Shagimardanova EI, Gazizova GR, Lysenko EA, Gusev OA, et al. Contractile activity-specific transcriptome response to acute endurance exercise and training in human skeletal muscle. American J Physiolog-Endocrinol Metabol. 2019;316(4):E605–14.CrossRef
25.
go back to reference Győrffy B. Survival analysis across the entire transcriptome identifies biomarkers with the highest prognostic power in breast cancer. Comput Struct Biotechnol J. 2021;19:4101–9.PubMedPubMedCentralCrossRef Győrffy B. Survival analysis across the entire transcriptome identifies biomarkers with the highest prognostic power in breast cancer. Comput Struct Biotechnol J. 2021;19:4101–9.PubMedPubMedCentralCrossRef
26.
go back to reference Sutherland A, Thomas M, Brandon RA, Brandon RB, Lipman J, Tang B, et al. Development and validation of a novel molecular biomarker diagnostic test for the early detection of sepsis. Crit Care. 2011;15(3):R149.PubMedPubMedCentralCrossRef Sutherland A, Thomas M, Brandon RA, Brandon RB, Lipman J, Tang B, et al. Development and validation of a novel molecular biomarker diagnostic test for the early detection of sepsis. Crit Care. 2011;15(3):R149.PubMedPubMedCentralCrossRef
27.
go back to reference Cazalis M-A, Lepape A, Venet F, Frager F, Mougin B, Vallin H, et al. Early and dynamic changes in gene expression in septic shock patients: a genome-wide approach. Intensive Care Med Exp. 2014;2(1):20.PubMedPubMedCentralCrossRef Cazalis M-A, Lepape A, Venet F, Frager F, Mougin B, Vallin H, et al. Early and dynamic changes in gene expression in septic shock patients: a genome-wide approach. Intensive Care Med Exp. 2014;2(1):20.PubMedPubMedCentralCrossRef
28.
go back to reference Venet F, Schilling J, Cazalis M-A, Demaret J, Poujol F, Girardot T, et al. Modulation of LILRB2 protein and mRNA expressions in septic shock patients and after ex vivo lipopolysaccharide stimulation. Hum Immunol. 2017;78(5):441–50.PubMedCrossRef Venet F, Schilling J, Cazalis M-A, Demaret J, Poujol F, Girardot T, et al. Modulation of LILRB2 protein and mRNA expressions in septic shock patients and after ex vivo lipopolysaccharide stimulation. Hum Immunol. 2017;78(5):441–50.PubMedCrossRef
29.
go back to reference Bhattacharya S, Dunn P, Thomas CG, Smith B, Schaefer H, Chen J, et al. ImmPort, toward repurposing of open access immunological assay data for translational and clinical research. Scientific Data. 2018;5(1):180015.PubMedPubMedCentralCrossRef Bhattacharya S, Dunn P, Thomas CG, Smith B, Schaefer H, Chen J, et al. ImmPort, toward repurposing of open access immunological assay data for translational and clinical research. Scientific Data. 2018;5(1):180015.PubMedPubMedCentralCrossRef
30.
go back to reference Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research. 2015;43(7):e47-e.CrossRef Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research. 2015;43(7):e47-e.CrossRef
31.
go back to reference Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023;51(D1):D587–92.PubMedCrossRef Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M. KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2023;51(D1):D587–92.PubMedCrossRef
34.
go back to reference Yu G, Wang L-G, Han Y, He Q-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. J Integrat Biol. 2012;16(5):284–7. Yu G, Wang L-G, Han Y, He Q-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. J Integrat Biol. 2012;16(5):284–7.
35.
go back to reference Szklarczyk D, Morris J, Cook H, Kuhn M, Wyder S, Simonovic M, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017;45(D1):D362–8.PubMedCrossRef Szklarczyk D, Morris J, Cook H, Kuhn M, Wyder S, Simonovic M, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017;45(D1):D362–8.PubMedCrossRef
36.
go back to reference Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.PubMedPubMedCentralCrossRef Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504.PubMedPubMedCentralCrossRef
37.
go back to reference Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010;38(2):W214–20. Warde-Farley D, Donaldson SL, Comes O, Zuberi K, Badrawi R, Chao P, et al. The GeneMANIA prediction server: biological network integration for gene prioritization and predicting gene function. Nucleic Acids Res. 2010;38(2):W214–20.
38.
go back to reference Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez J-C, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinform. 2011;12(1):77.CrossRef Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez J-C, et al. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinform. 2011;12(1):77.CrossRef
39.
go back to reference Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018;46(D1):D1074–82. Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018;46(D1):D1074–82.
40.
go back to reference Xia H, Wang F, Wang M, Wang J, Sun S, Chen M, et al. Maresin1 ameliorates acute lung injury induced by sepsis through regulating Th17/Treg balance. Life Sci. 2020;254:117773.PubMedCrossRef Xia H, Wang F, Wang M, Wang J, Sun S, Chen M, et al. Maresin1 ameliorates acute lung injury induced by sepsis through regulating Th17/Treg balance. Life Sci. 2020;254:117773.PubMedCrossRef
42.
go back to reference Wiersinga WJ, Leopold SJ, Cranendonk DR, van der Poll T. Host innate immune responses to sepsis. Virulence. 2014;5(1):36–44.PubMedCrossRef Wiersinga WJ, Leopold SJ, Cranendonk DR, van der Poll T. Host innate immune responses to sepsis. Virulence. 2014;5(1):36–44.PubMedCrossRef
43.
go back to reference Delano MJ, Ward PA. The immune system’s role in sepsis progression, resolution, and long-term outcome. Immunol Rev. 2016;274(1):330–53. Delano MJ, Ward PA. The immune system’s role in sepsis progression, resolution, and long-term outcome. Immunol Rev. 2016;274(1):330–53.
44.
go back to reference Yende S, Kellum JA, Talisa VB, Peck Palmer OM, Chang CCH, Filbin MR, et al. Long-term Host Immune Response Trajectories Among Hospitalized Patients With Sepsis. JAMA Network Open. 2019;2(8):e198686-e.CrossRef Yende S, Kellum JA, Talisa VB, Peck Palmer OM, Chang CCH, Filbin MR, et al. Long-term Host Immune Response Trajectories Among Hospitalized Patients With Sepsis. JAMA Network Open. 2019;2(8):e198686-e.CrossRef
45.
go back to reference Xie W, Chen L, Chen L, Kou Q. Silencing of long non-coding RNA MALAT1 suppresses inflammation in septic mice: role of microRNA-23a in the down-regulation of MCEMP1 expression. Inflamm Res. 2020;69(2):179–90.PubMedCrossRef Xie W, Chen L, Chen L, Kou Q. Silencing of long non-coding RNA MALAT1 suppresses inflammation in septic mice: role of microRNA-23a in the down-regulation of MCEMP1 expression. Inflamm Res. 2020;69(2):179–90.PubMedCrossRef
46.
go back to reference Zhou G, Yu L, Fang L, Yang W, Yu T, Miao Y, et al. CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD. Gut. 2018;67(6):1052.PubMedCrossRef Zhou G, Yu L, Fang L, Yang W, Yu T, Miao Y, et al. CD177+ neutrophils as functionally activated neutrophils negatively regulate IBD. Gut. 2018;67(6):1052.PubMedCrossRef
47.
48.
go back to reference Sinha P, Okoro C, Foell D, Freeze HH, Ostrand-Rosenberg S, Srikrishna G. Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J Immunol. 2008;181(7):4666.PubMedCrossRef Sinha P, Okoro C, Foell D, Freeze HH, Ostrand-Rosenberg S, Srikrishna G. Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells. J Immunol. 2008;181(7):4666.PubMedCrossRef
49.
go back to reference Uhel F, Azzaoui I, Grégoire M, Pangault C, Dulong J, Tadié JM, et al. Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in patients with sepsis. Am J Respir Crit Care Med. 2017;196(3):315–27.PubMedCrossRef Uhel F, Azzaoui I, Grégoire M, Pangault C, Dulong J, Tadié JM, et al. Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in patients with sepsis. Am J Respir Crit Care Med. 2017;196(3):315–27.PubMedCrossRef
50.
go back to reference Foell D, Wittkowski H, Kessel C, Lüken A, Weinhage T, Varga G, et al. Proinflammatory S100A12 can activate human monocytes via toll-like receptor 4. Am J Respir Crit Care Med. 2013;187(12):1324–34.PubMedCrossRef Foell D, Wittkowski H, Kessel C, Lüken A, Weinhage T, Varga G, et al. Proinflammatory S100A12 can activate human monocytes via toll-like receptor 4. Am J Respir Crit Care Med. 2013;187(12):1324–34.PubMedCrossRef
51.
go back to reference Toufiq M, Roelands J, Alfaki M, Syed AhamedKabeer B, Saadaoui M, Lakshmanan AP, et al. Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data. Immunol. 2020;161(4):291–302.CrossRef Toufiq M, Roelands J, Alfaki M, Syed AhamedKabeer B, Saadaoui M, Lakshmanan AP, et al. Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data. Immunol. 2020;161(4):291–302.CrossRef
52.
go back to reference Ma J, Wei K, Liu J, Tang K, Zhang H, Zhu L, et al. Glycogen metabolism regulates macrophage-mediated acute inflammatory responses. Nat Commun. 2020;11(1):1769.PubMedPubMedCentralCrossRef Ma J, Wei K, Liu J, Tang K, Zhang H, Zhu L, et al. Glycogen metabolism regulates macrophage-mediated acute inflammatory responses. Nat Commun. 2020;11(1):1769.PubMedPubMedCentralCrossRef
53.
go back to reference Lu Z, Tao G, Sun X, Zhang Y, Jiang M, Liu Y, et al. Association of blood glucose level and glycemic variability with mortality in sepsis patients during ICU hospitalization. Front Public Health. 2022;10:857368.PubMedPubMedCentralCrossRef Lu Z, Tao G, Sun X, Zhang Y, Jiang M, Liu Y, et al. Association of blood glucose level and glycemic variability with mortality in sepsis patients during ICU hospitalization. Front Public Health. 2022;10:857368.PubMedPubMedCentralCrossRef
54.
go back to reference Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306(23):2594–605.PubMedPubMedCentralCrossRef Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, et al. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306(23):2594–605.PubMedPubMedCentralCrossRef
55.
go back to reference Danahy DB, Strother RK, Badovinac VP, Griffith TS. Clinical and experimental sepsis impairs CD8 T-cell-mediated immunity. Crit Rev Immunol. 2016;36(1):57–74.PubMedPubMedCentralCrossRef Danahy DB, Strother RK, Badovinac VP, Griffith TS. Clinical and experimental sepsis impairs CD8 T-cell-mediated immunity. Crit Rev Immunol. 2016;36(1):57–74.PubMedPubMedCentralCrossRef
56.
go back to reference Spec A, Shindo Y, Burnham CA, Wilson S, Ablordeppey EA, Beiter ER, et al. T cells from patients with Candida sepsis display a suppressive immunophenotype. Critical care (London, England). 2016;20:15.PubMedCrossRef Spec A, Shindo Y, Burnham CA, Wilson S, Ablordeppey EA, Beiter ER, et al. T cells from patients with Candida sepsis display a suppressive immunophenotype. Critical care (London, England). 2016;20:15.PubMedCrossRef
57.
go back to reference Venet F, Demaret J, Blaise BJ, Rouget C, Girardot T, Idealisoa E, et al. IL-7 Restores T Lymphocyte Immunometabolic Failure in Septic Shock Patients through mTOR Activation. J Immunol. 2017;199(5):1606–15.PubMedCrossRef Venet F, Demaret J, Blaise BJ, Rouget C, Girardot T, Idealisoa E, et al. IL-7 Restores T Lymphocyte Immunometabolic Failure in Septic Shock Patients through mTOR Activation. J Immunol. 2017;199(5):1606–15.PubMedCrossRef
58.
go back to reference Xue M, Xie J, Liu L, Huang Y, Guo F, Xu J, et al. Early and dynamic alterations of Th2/Th1 in previously immunocompetent patients with community-acquired severe sepsis: a prospective observational study. J Transl Med. 2019;17(1):57.PubMedPubMedCentralCrossRef Xue M, Xie J, Liu L, Huang Y, Guo F, Xu J, et al. Early and dynamic alterations of Th2/Th1 in previously immunocompetent patients with community-acquired severe sepsis: a prospective observational study. J Transl Med. 2019;17(1):57.PubMedPubMedCentralCrossRef
59.
go back to reference Almansa R, Ortega A, Ávila-Alonso A, Heredia-Rodríguez M, Martín S, Benavides D, et al. Quantification of immune dysregulation by next-generation polymerase chain reaction to improve sepsis diagnosis in surgical patients. Ann Surg. 2019;269(3):545–53. Almansa R, Ortega A, Ávila-Alonso A, Heredia-Rodríguez M, Martín S, Benavides D, et al. Quantification of immune dysregulation by next-generation polymerase chain reaction to improve sepsis diagnosis in surgical patients. Ann Surg. 2019;269(3):545–53.
60.
go back to reference Cajander S, Bäckman A, Tina E, Strålin K, Söderquist B, Källman J. Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis. Crit Care. 2013;17(5):R223.PubMedPubMedCentralCrossRef Cajander S, Bäckman A, Tina E, Strålin K, Söderquist B, Källman J. Preliminary results in quantitation of HLA-DRA by real-time PCR: a promising approach to identify immunosuppression in sepsis. Crit Care. 2013;17(5):R223.PubMedPubMedCentralCrossRef
61.
go back to reference Almansa R, Heredia-Rodríguez M, Gomez-Sanchez E, Andaluz-Ojeda D, Iglesias V, Rico L, et al. Transcriptomic correlates of organ failure extent in sepsis. J Infect. 2015;70(5):445–56.PubMedCrossRef Almansa R, Heredia-Rodríguez M, Gomez-Sanchez E, Andaluz-Ojeda D, Iglesias V, Rico L, et al. Transcriptomic correlates of organ failure extent in sepsis. J Infect. 2015;70(5):445–56.PubMedCrossRef
62.
go back to reference Huang W, Morales JL, Gazivoda VP, August A. Nonreceptor tyrosine kinases ITK and BTK negatively regulate mast cell proinflammatory responses to lipopolysaccharide. J Allergy Clinic Immunol. 2016;137(4):1197–205.CrossRef Huang W, Morales JL, Gazivoda VP, August A. Nonreceptor tyrosine kinases ITK and BTK negatively regulate mast cell proinflammatory responses to lipopolysaccharide. J Allergy Clinic Immunol. 2016;137(4):1197–205.CrossRef
63.
go back to reference Lillemeier BF, Mörtelmaier MA, Forstner MB, Huppa JB, Groves JT, Davis MM. TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation. Nat Immunol. 2010;11(1):90–6.PubMedCrossRef Lillemeier BF, Mörtelmaier MA, Forstner MB, Huppa JB, Groves JT, Davis MM. TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation. Nat Immunol. 2010;11(1):90–6.PubMedCrossRef
64.
go back to reference Zeng XFJ, Yang Y, Zhao R, Yu Q, Qin H, Wei L, Ji P, Li H, Wu Z, Zhang J. Screening of key genes of sepsis and septic shock using bioinformatics analysis. J Inflamm Res. 2021;14:829–41.PubMedPubMedCentralCrossRef Zeng XFJ, Yang Y, Zhao R, Yu Q, Qin H, Wei L, Ji P, Li H, Wu Z, Zhang J. Screening of key genes of sepsis and septic shock using bioinformatics analysis. J Inflamm Res. 2021;14:829–41.PubMedPubMedCentralCrossRef
65.
go back to reference Balagopalan L, Malik H, McIntire KM, Garvey JA, Nguyen T, Rodriguez-Peña AB, et al. Bypassing ubiquitination enables LAT recycling to the cell surface and enhanced signaling in T cells. PLoS ONE. 2020;15(2):e0229036.PubMedPubMedCentralCrossRef Balagopalan L, Malik H, McIntire KM, Garvey JA, Nguyen T, Rodriguez-Peña AB, et al. Bypassing ubiquitination enables LAT recycling to the cell surface and enhanced signaling in T cells. PLoS ONE. 2020;15(2):e0229036.PubMedPubMedCentralCrossRef
67.
go back to reference Spiess C, Merchant M, Huang A, Zheng Z, Yang NY, Peng J, et al. Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies. Nat Biotechnol. 2013;31(8):753–8.PubMedCrossRef Spiess C, Merchant M, Huang A, Zheng Z, Yang NY, Peng J, et al. Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies. Nat Biotechnol. 2013;31(8):753–8.PubMedCrossRef
68.
go back to reference Atwell S, Ridgway JB, Wells JA, Carter P. Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library. J Mol Biol. 1997;270(1):26–35.PubMedCrossRef Atwell S, Ridgway JB, Wells JA, Carter P. Stable heterodimers from remodeling the domain interface of a homodimer using a phage display library. J Mol Biol. 1997;270(1):26–35.PubMedCrossRef
69.
go back to reference Sun LL, Ellerman D, Mathieu M, Hristopoulos M, Chen X, Li Y, et al. Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Scie Translat Medic. 2015;7(287):28770. Sun LL, Ellerman D, Mathieu M, Hristopoulos M, Chen X, Li Y, et al. Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Scie Translat Medic. 2015;7(287):28770.
70.
go back to reference Seimetz D, Lindhofer H, Bokemeyer C. Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010;36(6):458–67.PubMedCrossRef Seimetz D, Lindhofer H, Bokemeyer C. Development and approval of the trifunctional antibody catumaxomab (anti-EpCAM x anti-CD3) as a targeted cancer immunotherapy. Cancer Treat Rev. 2010;36(6):458–67.PubMedCrossRef
71.
go back to reference Long SA, Thorpe J, DeBerg HA, Gersuk V, Eddy J, Harris KM, et al. Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes. Sci Immunol. 2016;1(5):eaai7793. Long SA, Thorpe J, DeBerg HA, Gersuk V, Eddy J, Harris KM, et al. Partial exhaustion of CD8 T cells and clinical response to teplizumab in new-onset type 1 diabetes. Sci Immunol. 2016;1(5):eaai7793.
72.
go back to reference McDermott DF, Cheng S-C, Signoretti S, Margolin KA, Clark JI, Sosman JA, et al. The high-dose aldesleukin “select” trial: A trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2015;21(3):561–8.PubMedCrossRef McDermott DF, Cheng S-C, Signoretti S, Margolin KA, Clark JI, Sosman JA, et al. The high-dose aldesleukin “select” trial: A trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2015;21(3):561–8.PubMedCrossRef
73.
go back to reference Kandus A, Arnol M, Omahen K, Oblak M, Vidan-Jeras B, Kmetec A, et al. Basiliximab versus daclizumab combined with triple immunosuppression in deceased donor renal transplantation: a prospective, randomized study. Transplantation. 2010;89(8):1022–7.PubMedCrossRef Kandus A, Arnol M, Omahen K, Oblak M, Vidan-Jeras B, Kmetec A, et al. Basiliximab versus daclizumab combined with triple immunosuppression in deceased donor renal transplantation: a prospective, randomized study. Transplantation. 2010;89(8):1022–7.PubMedCrossRef
74.
go back to reference Vargas L, Hamasy A, Nore BF, Smith CI. Inhibitors of BTK and ITK: state of the new drugs for cancer, autoimmunity and inflammatory diseases. Scand J Immunol. 2013;78(2):130–9.PubMedCrossRef Vargas L, Hamasy A, Nore BF, Smith CI. Inhibitors of BTK and ITK: state of the new drugs for cancer, autoimmunity and inflammatory diseases. Scand J Immunol. 2013;78(2):130–9.PubMedCrossRef
75.
go back to reference Verheijen RB, Beijnen JH, Schellens JHM, Huitema ADR, Steeghs N. Clinical pharmacokinetics and Pharmacodynamics of Pazopanib: towards optimized dosing. Clin Pharmacokinet. 2017;56(9):987–97.PubMedPubMedCentralCrossRef Verheijen RB, Beijnen JH, Schellens JHM, Huitema ADR, Steeghs N. Clinical pharmacokinetics and Pharmacodynamics of Pazopanib: towards optimized dosing. Clin Pharmacokinet. 2017;56(9):987–97.PubMedPubMedCentralCrossRef
Metadata
Title
Exploring the biomarkers and potential therapeutic drugs for sepsis via integrated bioinformatic analysis
Authors
Pingping Liang
Yongjian Wu
Siying Qu
Muhammad Younis
Wei Wang
Zhilong Wu
Xi Huang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2024
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-023-08883-9

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