Clinical trial NCT05524376: Regulatory Network and Diagnostic Value of Key Autophagy-related Genes in Sepsis
Official title: Regulatory Network and Diagnostic Value of Key Autophagy-related Genes in Sepsis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sepsis
Autophagy
Keywords: sepsis
autophagy
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2022-09-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: sepsis group: Eligible patients with sepsis admitted to the ICU of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from September 2022 to December 2022.

control group: Age - and sex-matched healthy controls.

Brief summary: Autophagy plays an important role in the occurrence and development of sepsis. This study aims to explore and verify the key autophagy-related genes in sepsis, then construct their regulatory networks and evaluate their potential diagnostic value, so as to provide new ideas for the diagnosis and treatment of sepsis.

Detailed description: (1) Sepsis-related datasets GSE65682,GSE134347 and GSE134358 were downloaded from GEO database, and DEmRNA,DElncRNA and DEmiRNA were obtained by differential analysis. (2) Autophagy related genes (ARGs) were obtained from Human Autophagy Database, and ARGs in GSE65682 and GSE134347 were extracted. DEARGs were obtained by differential analysis, and GO and KEGG enrichment analysis were performed. (3) Sepsis-related genes were obtained by WGCNA analysis, and key DEARGs in sepsis were obtained by intersection with DEARGs, and then transcription factors and ceRNA regulatory network were analyzed. (4) Immune infiltration analysis was used to evaluate the distribution of immune cells in the blood of patients with sepsis, and its correlation with key DEARGs was further analyzed. (5) The diagnostic functions of key DEARGs were analyzed. (6) Peripheral blood samples from sepsis patients and healthy controls were collected and verified by RT-qPCR.

Eligibility criteria: Inclusion Criteria:1) over 18 years old; 2) Meeting the diagnostic criteria of Sepsis 3.0; 3) Hospital stay longer than 24 hours.

Exclusion Criteria:1) Malignant tumor; 2) Autoimmune diseases; 3) Use of immunosuppressants in the past two weeks; 4) Readmission or transfer from another ICU due to the same disease.

Primary outcomes:
measure: Diagnostic Value of Key Autophagy-related Genes in Sepsis
timeFrame: October 2022
measure: Regulatory Network of Key Autophagy-related Genes in Sepsis
timeFrame: October 2022
measure: Verified Key Autophagy-related Genes in Sepsis by RT-qPCR.
timeFrame: December 2022
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
citation: Takahashi W, Watanabe E, Fujimura L, Watanabe-Takano H, Yoshidome H, Swanson PE, Tokuhisa T, Oda S, Hatano M. Kinetics and protective role of autophagy in a mouse cecal ligation and puncture-induced sepsis. Crit Care. 2013 Jul 24;17(4):R160. doi: 10.1186/cc12839.
citation: Aguirre A, Lopez-Alonso I, Gonzalez-Lopez A, Amado-Rodriguez L, Batalla-Solis E, Astudillo A, Blazquez-Prieto J, Fernandez AF, Galvan JA, dos Santos CC, Albaiceta GM. Defective autophagy impairs ATF3 activity and worsens lung injury during endotoxemia. J Mol Med (Berl). 2014 Jun;92(6):665-76. doi: 10.1007/s00109-014-1132-7. Epub 2014 Feb 19.
citation: Oami T, Watanabe E, Hatano M, Sunahara S, Fujimura L, Sakamoto A, Ito C, Toshimori K, Oda S. Suppression of T Cell Autophagy Results in Decreased Viability and Function of T Cells Through Accelerated Apoptosis in a Murine Sepsis Model. Crit Care Med. 2017 Jan;45(1):e77-e85. doi: 10.1097/CCM.0000000000002016.