Regulatory Network and Diagnostic Value of Key Autophagy-related Genes in Sepsis

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Autophagy
• Intervention / Treatment: Other: no intervention

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.

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Zhijie He; Phone Number: 13710898290; Email: hezhijie2004@126.com
• Study Contact Backup: Name: Li Yang; Phone Number: 15254586586; Email: 375948656@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
control group	Other: no intervention; no intervention
sepsis group	Other: no intervention; no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Value of Key Autophagy-related Genes in Sepsis	The diagnostic functions of key DEARGs (Differential Autophagy-related Genes) were analyzed	October 2022
Regulatory Network of Key Autophagy-related Genes in Sepsis	Key DEARGs in sepsis were analyzed for transcription factors and ceRNA regulatory network	October 2022
Verified Key Autophagy-related Genes in Sepsis by RT-qPCR.	Peripheral blood samples from sepsis patients and healthy controls were collected and verified by RT-qPCR.	December 2022

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2022
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 1, 2022

Study Record Updates

• Last Update Posted (Actual): September 1, 2022
• Last Update Submitted That Met QC Criteria: August 30, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: sepsis; autophagy
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: SYSKY-2022-251-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No