Download PDF
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)
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

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.

Keywords

platelets - sepsis - prognosis - diagnosis - human leukocyte antigen

Supplementary Material



Publication History

Received: 22 February 2024

Accepted after revision: 15 May 2024

Article published online:
13 June 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
    CrossrefPubMedGoogle Scholar
  • 2 Huang M, Cai S, Su J. The pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci 2019; 20: 5376
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 5 Vincent JL, Yagushi A, Pradier O. Platelet function in sepsis. Crit Care Med 2002; 30: S313-S317
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 7 Greco E, Lupia E, Bosco O. et al. Platelets and multi-organ failure in sepsis. Int J Mol Sci 2017; 18: 2200
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 12 Vickers AJ, Elkin EB. Decision curve analysis: a novel method for evaluating prediction models. Med Decis Making 2006; 26: 565-574
    CrossrefPubMedGoogle Scholar
  • 13 van der Poll T, Shankar-Hari M, Wiersinga WJ. The immunology of sepsis. Immunity 2021; 54: 2450-2464
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 17 Mas-Celis F, Olea-Lopez J, Parroquin-Maldonado JA. Sepsis in trauma: a deadly complication. Arch Med Res 2021; 52: 808-816
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 20 Olsen Saraiva Camara N, Lepique AP, Basso AS. Lymphocyte differentiation and effector functions. Clin Dev Immunol. 2012 510603. DOI: 10.1155/2012/510603
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 23 Chavakis E, Choi EY, Chavakis T. Novel aspects in the regulation of the leukocyte adhesion cascade. Thromb Haemost 2009; 102: 191-197
    Article in Thieme ConnectPubMedGoogle Scholar
  • 24 Kovach MA, Standiford TJ. The function of neutrophils in sepsis. Curr Opin Infect Dis 2012; 25: 321-327
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 29 Baltanas FC, Zarich N, Rojas-Cabaneros JM. et al. SOS GEFs in health and disease. Biochim Biophys Acta Rev Cancer 2020; 1874: 188445
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 35 Fortner A, Chera A, Tanca A. et al. Apoptosis regulation by the tyrosine-protein kinase CSK. Front Cell Dev Biol 2022; 10: 1078180
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 44 Ibrahim AM, Gray Z, Gomes AM. et al. Gas6 expression is reduced in advanced breast cancers. NPJ Precis Oncol 2020; 4: 9
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 46 Gibot S, Massin F, Cravoisy A. et al. Growth arrest-specific protein 6 plasma concentrations during septic shock. Crit Care 2007; 11: R8
    CrossrefPubMedGoogle Scholar
  • 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.
    PubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar