Horm Metab Res
DOI: 10.1055/a-2331-1362
Original Article: Endocrine Research

Prediction of Prognosis in Patients with Sepsis Based on Platelet-Related Genes

Jing Jiang
1   Intensive Care Unit, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, China (Ringgold ID: RIN590552)
,
Juan Zhang
2   Cardiology, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, China (Ringgold ID: RIN590552)
,
Ting Wang
3   Endocrinology, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, China (Ringgold ID: RIN590552)
,
Daihua Yu
1   Intensive Care Unit, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, China (Ringgold ID: RIN590552)
,
Xiu Ren
1   Intensive Care Unit, Xi'an No.3 Hospital, the Affiliated Hospital of Northwest University, Xi'an, China (Ringgold ID: RIN590552)
› Institutsangaben

Abstract

The study aimed to develop a risk prognostic model using platelet-related genes (PRGs) to predict sepsis patient outcomes. Sepsis patient data from the Gene Expression Omnibus (GEO) database and PRGs from the Molecular Signatures Database (MSigDB) were analyzed. Differential analysis identified 1139 differentially expressed genes (DEGs) between sepsis and control groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed enrichment in functions related to immune cell regulation and pathways associated with immune response and infectious diseases. A risk prognostic model was established using LASSO and Cox regression analyses, incorporating 10 PRGs selected based on their association with sepsis prognosis. The model demonstrated good stratification and prognostic effects, confirmed by survival and receiver operating characteristic (ROC) curve analyses. It served as an independent prognostic factor in sepsis patients. Further analysis using the CIBERSORT algorithm showed higher infiltration of activated natural killer (NK) cells and lower infiltration of CD8 T cells and CD4 T cells naïve in the high-risk group compared to the low-risk group. Additionally, expression levels of human leukocyte antigen (HLA) genes were significantly lower in the high-risk group. In conclusion, the 10-gene risk model based on PRGs accurately predicted sepsis patient prognosis and immune infiltration levels. This study provides valuable insights into the role of platelets in sepsis prognosis and diagnosis, offering potential implications for personalized treatment strategies.

Supplementary Material



Publikationsverlauf

Eingereicht: 22. Februar 2024

Angenommen nach Revision: 15. Mai 2024

Artikel online veröffentlicht:
13. Juni 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Salomao R, Ferreira BL, Salomao MC. et al. Sepsis: evolving concepts and challenges. Braz J Med Biol Res 2019; 52: e8595
  • 2 Huang M, Cai S, Su J. The pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci 2019; 20: 5376
  • 3 Bauer M, Gerlach H, Vogelmann T. et al. Mortality in sepsis and septic shock in Europe, North America and Australia between 2009 and 2019- results from a systematic review and meta-analysis. Crit Care 2020; 24: 239
  • 4 Wattal C, Kler N, Oberoi JK. et al. Neonatal sepsis: mortality and morbidity in neonatal sepsis due to multidrug-resistant (MDR) organisms: Part 1. Indian J Pediatr 2020; 87: 117-121
  • 5 Vincent JL, Yagushi A, Pradier O. Platelet function in sepsis. Crit Care Med 2002; 30: S313-S317
  • 6 Valet C, Magnen M, Qiu L. et al. Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression. J Clin Invest 2022; 132: e153920
  • 7 Greco E, Lupia E, Bosco O. et al. Platelets and multi-organ failure in sepsis. Int J Mol Sci 2017; 18: 2200
  • 8 Wang D, Wang S, Wu H. et al. Association between platelet levels and 28-day mortality in patients with sepsis: a retrospective analysis of a lLarge clinical database MIMIC-IV. Front Med (Lausanne) 2022; 9: 833996
  • 9 Cai N, Chen ZQ, Tao M. et al. Mean platelet volume and red blood cell distribution width is associated with prognosis in premature neonates with sepsis. Open Med (Wars) 2021; 16: 1175-1181
  • 10 Orfanu AE, Popescu C, Leustean A. et al. The importance of haemogram parameters in the diagnosis and prognosis of septic patients. J Crit Care Med (Targu Mures) 2017; 3: 105-110
  • 11 Li X, Zhao K, Lu Y. et al. Genetic analysis of platelet-related genes in hepatocellular carcinoma reveals a novel prognostic signature and determines PRKCD as the potential molecular bridge. Biol Proced Online 2022; 24: 22
  • 12 Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making 2006; 26: 565-574
  • 13 van der Poll T, Shankar-Hari M, Wiersinga WJ. The immunology of sepsis. Immunity 2021; 54: 2450-2464
  • 14 Horn DL, Mindrinos M, Anderson K. et al. HLA-A locus is associated with sepsis and septic shock after traumatic injury. Ann Surg 2022; 275: 203-207
  • 15 Zhuang Y, Peng H, Chen Y. et al. Dynamic monitoring of monocyte HLA-DR expression for the diagnosis, prognosis, and prediction of sepsis. Front Biosci (Landmark Ed) 2017; 22: 1344-1354
  • 16 Wilhelms SB, Walther SM, Sjoberg F. et al. Causes of late mortality among ICU-treated patients with sepsis. Acta Anaesthesiol Scand 2020; 64: 961-966
  • 17 Mas-Celis F, Olea-Lopez J, Parroquin-Maldonado JA. Sepsis in trauma: a deadly complication. Arch Med Res 2021; 52: 808-816
  • 18 Cao Y, Ma W, Liu Z. et al. Early predictive value of platelet function for clinical outcome in sepsis. J Infect 2022; 84: 628-636
  • 19 Zhang C, Shang X, Yuan Y. et al. Platelet‑related parameters as potential biomarkers for the prognosis of sepsis. Exp Ther Med 2023; 25: 133
  • 20 Olsen Saraiva Camara N, Lepique AP, Basso AS. Lymphocyte differentiation and effector functions. Clin Dev Immunol. 2012 510603. DOI: 10.1155/2012/510603
  • 21 Chen L, Ke H, Zhang Y. et al. Orai1 overexpression improves sepsis-induced T-lymphocyte immunosuppression and acute organ dysfunction in mice. Heliyon 2022; 8: e12082
  • 22 Ma Y, Cheng Z, Zheng Y. et al. Low dose of esmolol attenuates sepsis-induced immunosuppression via modulating T-lymphocyte apoptosis and differentiation. Shock 2023; 59: 771-778
  • 23 Chavakis E, Choi EY, Chavakis T. Novel aspects in the regulation of the leukocyte adhesion cascade. Thromb Haemost 2009; 102: 191-197
  • 24 Kovach MA, Standiford TJ. The function of neutrophils in sepsis. Curr Opin Infect Dis 2012; 25: 321-327
  • 25 Fang X, Duan SF, Hu ZY. et al. Inhibition of matrix metalloproteinase-8 protects against sepsis serum mediated leukocyte adhesion. Front Med (Lausanne) 2022; 9: 814890
  • 26 Le Menn G, Jablonska A, Chen Z. The effects of post-translational modifications on Th17/Treg cell differentiation. Biochim Biophys Acta Mol Cell Res 2022; 1869: 119223
  • 27 Zhang W, Chen B, Chen W. LncRNA GAS5 relates to Th17 cells and serves as a potential biomarker for sepsis inflammation, organ dysfunctions and mortality risk. J Clin Lab Anal 2022; 36: e24309
  • 28 Liu C, Zou Q. miR-21 regulates immune balance mediated by Th17/Treg in peripheral blood of septic rats during the early phase through apoptosis pathway. Biochem Res Int. 2022 9948229. DOI: 10.1155/2022/9948229
  • 29 Baltanas FC, Zarich N, Rojas-Cabaneros JM. et al. SOS GEFs in health and disease. Biochim Biophys Acta Rev Cancer 2020; 1874: 188445
  • 30 Xue M, Zhang S, Xie J. et al. Differential expression of genes associated with T lymphocytes function in septic patients with hypoxemia challenge. Ann Transl Med 2019; 7: 810
  • 31 An H, Ordureau A, Paulo JA. et al. TEX264 is an endoplasmic reticulum-resident ATG8-interacting protein critical for ER remodeling during nutrient stress. Mol Cell 2019; 74: 891-908 e810
  • 32 Wang Z, Huang J, Yang SP. et al. Anti-inflammatory anthranilate analogue enhances autophagy through mTOR and promotes ER-turnover through TEX264 during Alzheimer-associated Nneuroinflammation. ACS Chem Neurosci 2022; 13: 406-422
  • 33 Li H, Hu D, Fan H. et al. beta-Arrestin 2 negatively regulates toll-like receptor 4 (TLR4)-triggered inflammatory signaling via targeting p38 MAPK and interleukin 10. J Biol Chem 2014; 289: 23075-23085
  • 34 Zhou Y, Song Y, Shaikh Z. et al. MicroRNA-155 attenuates late sepsis-induced cardiac dysfunction through JNK and beta-arrestin 2. Oncotarget 2017; 8: 47317-47329
  • 35 Fortner A, Chera A, Tanca A. et al. Apoptosis regulation by the tyrosine-protein kinase CSK. Front Cell Dev Biol 2022; 10: 1078180
  • 36 Gupta S, Lee CM, Wang JF. et al. Heat-shock protein-90 prolongs septic neutrophil survival by protecting c-Src kinase and caspase-8 from proteasomal degradation. J Leukoc Biol 2018; 103: 933-944
  • 37 Kumar Singh P, Kashyap A, Silakari O. Exploration of the therapeutic aspects of Lck: A kinase target in inflammatory mediated pathological conditions. Biomed Pharmacother 2018; 108: 1565-1571
  • 38 Zhou X, Wang Y, Chen J. et al. Constructing a 10-core genes panel for diagnosis of pediatric sepsis. J Clin Lab Anal 2021; 35: e23680
  • 39 Chen M, Chen X, Hu Y. et al. Screening of key genes related to the prognosis of mouse sepsis. Biosci Rep 2020; 40: BSR20202649
  • 40 Li M, Huang H, Ke C. et al. Identification of a novel four-gene diagnostic signature for patients with sepsis by integrating weighted gene co-expression network analysis and support vector machine algorithm. Hereditas 2022; 159: 14
  • 41 Cheng YL, Ding ZX, Cao LJ. et al. [Gene diagnosis of a family with coagulation factor XIII deficiency caused by large deletion of F13A1 gene]. Zhonghua Xue Ye Xue Za Zhi 2023; 44: 62-65
  • 42 Shapland C, Hsuan JJ, Totty NF. et al. Purification and properties of transgelin: a transformation and shape change sensitive actin-gelling protein. J Cell Biol 1993; 121: 1065-1073
  • 43 Tian X, Li L, Fu G. et al. miR-133a-3p regulates the proliferation and apoptosis of intestinal epithelial cells by modulating the expression of TAGLN2. Exp Ther Med 2021; 22: 824
  • 44 Ibrahim AM, Gray Z, Gomes AM. et al. Gas6 expression is reduced in advanced breast cancers. NPJ Precis Oncol 2020; 4: 9
  • 45 Zweemer AJM, French CB, Mesfin J. et al. Apoptotic bodies elicit gas6-mediated migration of AXL-expressing tumor cells. Mol Cancer Res 2017; 15: 1656-1666
  • 46 Gibot S, Massin F, Cravoisy A. et al. Growth arrest-specific protein 6 plasma concentrations during septic shock. Crit Care 2007; 11: R8
  • 47 Salmi L, Gavelli F, Patrucco F. et al. Gas6/TAM axis in sepsis: time to consider its potential role as a therapeutic target. Dis Markers. 2019 6156493.
  • 48 Feng T, Liao X, Yang X. et al. A shift toward inhibitory receptors and impaired effector functions on NK cells contribute to immunosuppression during sepsis. J Leukoc Biol 2020; 107: 57-67
  • 49 Ma L, Li Q, Cai S. et al. The role of NK cells in fighting the virus infection and sepsis. Int J Med Sci 2021; 18: 3236-3248
  • 50 Yan L, Chen Y, Han Y. et al. Role of CD8(+) T cell exhaustion in the progression and prognosis of acute respiratory distress syndrome induced by sepsis: a prospective observational study. BMC Emerg Med 2022; 22: 182
  • 51 Chen J, Wang H, Guo R. et al. Early expression of functional markers on CD4(+) T cells predicts outcomes in ICU patients with Sepsis. Front Immunol 2022; 13: 938538