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Review | Open Access

Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets

Mingzheng Wu1,† , Bobin Mi2,†, Liu Liu3,†, Haoli Ma4, Cheng Jiang1, Shan Jiang1, Yulin Li1, Yan Zhao1( )
Emergency Medicine Center, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuchang District, Wuhan 430061, China
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China
College of Education of Hubei University, 368 Youyi Avenue, Wuchang District, Wuhan 430062, Hubei Province, China
Department of Biological Repositories, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuchang District, Wuhan 430071, Hubei Province, China

†Mingzheng Wu, Bobin Mi and Liu Liu contributed equally to this work.

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Highlights

• Pathogenic genes are known to cause septic shock through specific alleles, while protective genes have been found to confer beneficial effects on affected individuals.

• Despite the existence of many biomarkers linked to septic shock, their clinical utilization remains limited.

• Septic shock is closely associated with multiple signaling pathways, including TLR2/TLR4, TNF-α, PI3K/AKT,MAPK, NF-κB, JAK/STAT, mTOR, NLRP3 and HIF-1.

Abstract

Septic shock is a severe form of sepsis characterized by high global mortality rates and significant heritability. Clinicians have long been perplexed by the differential expression of genes, which poses challenges for early diagnosis and prompt treatment of septic shock. Genetic polymorphisms play crucial roles in determining susceptibility to, mortality from, and the prognosis of septic shock. Research indicates that pathogenic genes are known to cause septic shock through specific alleles, and protective genes have been shown to confer beneficial effects on affected individuals. Despite the existence of many biomarkers linked to septic shock, their clinical use remains limited. Therefore, further investigation is needed to identify specific biomarkers that can facilitate early prevention, diagnosis and risk stratification. Septic shock is closely associated with multiple signaling pathways, including the toll-like receptor 2/toll-like receptor 4, tumor necrosis factor-α, phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, nuclear factor κB, Janus kinase/signal transducer and activator of transcription, mammalian target of rapamycin, NOD-like receptor thermal protein domain-associated protein 3 and hypoxia-induced-factor-1 pathways. Understanding the regulation of these signaling pathways may lead to the identification of therapeutic targets for the development of novel drugs to treat sepsis or septic shock. In conclusion, identifying differential gene expression during the development of septic shock allows physicians to stratify patients according to risk at an early stage. Furthermore, auxiliary examinations can assist physicians in identifying therapeutic targets within relevant signaling pathways, facilitating early diagnosis and treatment, reducing mortality and improving the prognosis of septic shock patients. Although there has been significant progress in studying the genetic polymorphisms, specific biomarkers and signaling pathways involved in septic shock, the journey toward their clinical application and widespread implementation still lies ahead.

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Burns & Trauma
Article number: tkae006

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Cite this article:
Wu M, Mi B, Liu L, et al. Genetic polymorphisms, biomarkers and signaling pathways associated with septic shock: from diagnosis to therapeutic targets. Burns & Trauma, 2024, 12: tkae006. https://doi.org/10.1093/burnst/tkae006

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Received: 08 July 2023
Revised: 13 November 2023
Accepted: 01 February 2024
Published: 10 October 2026
© The Author(s) 2024. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.