|
|
Screening of key genes for death in sepsis patients based on bioinformatics method |
TAN Mingming1 ZHANG Jinming1 DENG Yisi1 ZHAO Fengli2 LUO Yuanyuan2 |
1.The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangdong Province, Guangzhou 510000, China; 2.Department of Critical Care Medicine, the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong Province, Guangzhou 510000, China |
|
|
Abstract Objective To screen and analyze the key genes for death in sepsis patients by bioinformatics method, and to provide a new idea for the basic research of sepsis. Methods The gene pool related to sepsis was searched in GEO database by computer, and the database GSE54514 with peripheral blood gene profile of sepsis patients was selected, and then differential gene analysis, including GO and KEGG enrichment analysis, was performed. The protein protein interaction (PPI) network of differential genes was established using the STRING database, and finally Cytoscape software was used to analyze the interactions of differential genes and screen out the top ten genes that may be associated with death in sepsis patients. After that, the differential genes of sepsis patients and healthy people were screened through another sepsis gene profile GSE137342, and the common differential genes of the two parts of differential genes were found out, and then analyzed in detail. Results There were 184 differential genes (92 up-regulated genes and 92 down-regulated genes) between the patients who died of sepsis and those who did not die of sepsis detected by GSE54514, and the differences were statistically significant (P<0.05). The results of GO enrichment analysis suggested that the biological processes of these differential genes were mainly concentrated in the generation of precursor metabolites and energy, negative regulation of protein complex assembly, ATP metabolism, and so on. The cell components were mainly concentrated in the adhesive plaque, cyst cavity, cytoplasmic cyst cavity, and so on. The molecular functions were mainly concentrated in cadherin binding, ribosome structural components, integrin binding, and so on. KEGG enrichment analysis indicated that these differential gene pathways were mainly enriched in diabetic cardiomyopathy, ribosome, and so on. The PPI network was used to identify the top ten key genes associated with death in patients with sepsis, including RPS17, RPS15A, RPL27, RPS27, FAU, etc. According to GSE137342, 623 differential genes (seven up-regulated genes and 616 down-regulated genes) were detected between sepsis patients and healthy people, and the differences were statistically significant (P<0.05). The two databases shared 16 differential genes. Compared with the top ten key genes related to the death of sepsis patients, it was found that RPL27, RPS27, and FAU were the common differential genes. Conclusion RPL27, RPS27, and FAU may be involved in the pathophysiological process of sepsis development and prognosis, and are closely related to the death outcome of sepsis patients.
|
|
|
|
|
[1] Evans L,Rhodes A,Alhazzani W,et al. Surviving Sepsis Campaign:International Guidelines for Management of Sepsis and Septic Shock 2021 [J]. Crit Care Med,2021,49(11):e1063- e1143. [2] Singer M,Deutschman CS,Seymour CW,et al. The Third Inter- national Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)[J]. JAMA,2016,315(8):801-810. [3] Liu YC,Yao Y,Yu MM,et al. Frequency and mortality of sepsis and septic shock in China:a systematic review and meta- an- alysis [J]. BMC Infect Dis,2022,22(1):564. [4] Egi M,Ogura H,Yatabe T,et al. The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020(J-SSCG 2020)[J]. Acute Med Surg,2021,8(1):e659. [5] Kim J,Kim K,Lee H,et al. Epidemiology of sepsis in Korea:a population-based study of incidence,mortality,cost and risk factors for death in sepsis [J]. Clin Exp Emerg Med,2019, 6(1):49-63. [6] 李维勤.脓毒症诊疗的新挑战:持续炎症、免疫抑制和分解代谢综合征[J].医学研究生学报,2017,30(7):673- 677. [7] Levi M,van der Poll T. Coagulation and sepsis [J]. Thromb Res,2017(149):38-44. [8] 廖明喻,刘雪健,武免免,等.脓毒症病理生理机制及治疗新方法的探索[J].医学综述,2019,25(3):475-479. [9] 于中锴,张宗旺,菅向东.脓毒症的研究进展[J].中华卫生应急电子杂志,2019,5(2):118-121. [10] 姚咏明,张艳敏.脓毒症发病机制最新认识[J].医学研究生学报,2017,30(7):678-683. [11] 刘铭传,李林成,白晓智.脓毒症病理生理及信号转导机制的研究进展[J].中华医院感染学杂志,2019,29(22):3511-3514,3520. [12] Namath A,Patterson AJ. Genetic polymorphisms in sepsis [J]. Crit Care Nurs Clin North Am,2011,23(1):181-202. [13] Yu X,Qu C,Ke L,et al. Step-by-Step Construction of Gene Co-Expression Network Analysis for Identifying Novel Biomarkers of Sepsis Occurrence and Progression [J]. Int J Gen Med,2021,14:6047-6057. [14] Fu Q,Yu W,Fu S,et al. Screening and identification of key gene in sepsis development:Evidence from bioinformatics analysis [J]. Medicine(Baltimore),2020,99(27):e20759. [15] Qi Y,Chen X,Wu N,et al. Identification of risk factors for sepsis-associated mortality by gene expression profiling analysis [J]. Mol Med Rep,2018,17(4):5350-5355. [16] Davies SM,Lopez Sanchez MI,Narsai R,et al. MRPS27 is a pentatricopeptide repeat domain protein required for the translation of mitochondrially encoded proteins [J]. FEBS Lett,2012,586(20):3555-3561. [17] Wang R,Yoshida K,Toki T,et al. Loss of function mutations in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan anaemia [J]. Br J Haematol,2015, 168(6):854-864. [18] Tao L,Ma J,Han L,et al. Early postmortem interval estima- tion based on Cdc25b mRNA in rat cardiac tissue [J]. Leg Med(Tokyo),2018,35:18-24. [19] Bu L,Wang ZW,Hu SQ,et al. Identification of Key mRNAs and lncRNAs in Neonatal Sepsis by Gene Expression Pro- filing [J]. Comput Math Methods Med,2020,2020:8741739. [20] Cappadocia L,Lima CD. Ubiquitin-like Protein Conjugation:Structures,Chemistry,and Mechanism [J]. Chem Rev,2018, 118(3):889-918. [21] Bloos F,Held J,Kluge S,et al.(1→3)-β-D-Glucan-guided antifungal therapy in adults with sepsis:the CandiSep randomized clinical trial [J]. Intensive Care Med,2022,48(7):865-875. [22] Bénard A,Hansen FJ,Uhle F,et al. Interleukin-3 protects against viral pneumonia in sepsis by enhancing plasm- acytoid dendritic cell recruitment into the lungs and T cell priming [J]. Front Immunol,2023,14:1140630. [23] Amar N,Lustig G,Ichimura Y,et al. Two newly identified sites in the ubiquitin-like protein Atg8 are essential for autophagy [J]. EMBO Rep,2006,7(6):635-642. [24] Perng YC,Lenschow DJ. ISG15 in antiviral immunity and beyond [J]. Nat Rev Microbiol,2018,16(7):423-439. [25] Streich FC Jr,Lima CD. Structural and functional insights to ubiquitin-like protein conjugation [J]. Annu Rev Biophys,2014,43:357-379. [26] Ross MJ,Wosnitzer MS,Ross MD,et al. Role of ubiquitin- like protein FAT10 in epithelial apoptosis in renal disease [J]. J Am Soc Nephrol,2006,17(4):996-1004. [27] He SY,Wang G,Pei YH,et al. miR-34b-3p protects against acute kidney injury in sepsis mice via targeting ubiquitin- like protein 4A [J]. Kaohsiung J Med Sci,2020,36(10):817-824. [28] Si X,Cao D,Chen J,et al. miR-23a downregulation modu- lates the inflammatory response by targeting ATG12 medi- ated autophagy [J]. Mol Med Rep,2018,18(2):1524-1530. |
|
|
|