MicroRNAs combined with the TLR4/TDAG8 mRNAs and proinflammatory cytokines are biomarkers for the rapid diagnosis of sepsis

Xu,Xiyuan; Bu,Baoying; Tian,Hongjun; Wu,Rina; Yang,Jingping

doi:10.3892/mmr.2022.12850

MicroRNAs combined with the TLR4/TDAG8 mRNAs and proinflammatory cytokines are biomarkers for the rapid diagnosis of sepsis

Authors:
- Xiyuan Xu
- Baoying Bu
- Hongjun Tian
- Rina Wu
- Jingping Yang
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Affiliations: Department of Respiratory and Critical Medicine, Third Affiliated Hospital, Inner Mongolia Medical University, Baotou, Inner Mongolia Autonomous Region 014010, P.R. China
Published online on: September 12, 2022 https://doi.org/10.3892/mmr.2022.12850
Article Number: 334
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The early diagnosis and treatment of sepsis are of particular importance to patient survival. To obtain novel biomarkers that serve as prompt indicators of sepsis, the current study screened the differentially expressed microRNAs (DEMs) that were associated with sepsis susceptibility. The correlation between the elucidated DEMs and the inflammatory response was also examined. The present study included 40 patients with sepsis and 40 healthy controls. RNA‑sequencing technology and bioinformatics analysis were applied to screen the DEMs between the two cohorts. The expression of these DEMs was subsequently verified by performing reverse transcription‑quantitative PCR (RT‑qPCR). In addition, IL‑6, IL‑21, C‑X‑C motif chemokine ligand‑8 (CXCL8) and monocyte chemoattractant protein‑1 (MCP‑1) levels, along with T‑cell death‑associated gene 8 (TDAG8) and toll‑like receptor 4 (TLR4) mRNA expression levels were assessed. The association between microRNA (miRNA/miR)‑3663‑3p and the secretion of various proinflammatory cytokines or TDAG8 and TLR4 mRNA expressions were subsequently evaluated by linear correlation analysis. The results revealed 305 DEMs (P<0.05; fold change >2) between patients with sepsis and healthy controls. Among these, the top 18 up‑ and downregulated miRNAs were selected for RT‑qPCR verification. In addition, the serum content of IL‑6, IL‑21, CXCL8 and MCP‑1, and the expression of TDAG8 and TLR4 mRNAs were significantly increased in patients with sepsis compared with healthy controls. Moreover, in patients with sepsis, a positive correlation was identified between miR‑3663‑3p and the secretion of inflammatory cytokines or TDAG8 and TLR4 mRNA expression. A positive correlation was also elucidated between TDAG8 and TLR4 mRNA expression and proinflammatory cytokine/chemokine secretion. Receiver operating characteristic curve analysis of miR‑3663‑3p expression, IL‑6, IL‑21, CXCL8 and MCP‑1 secretion and TDAG8 and TLR4 mRNA expression demonstrated that miRNA analysis may be invaluable for the diagnosis of sepsis. Collectively, the results determined that miR‑3663‑3p may be a potentially powerful diagnostic and predictive biomarker of sepsis and that the combined and simultaneous detection of several biomarkers, including proteins, miRNAs and mRNA may be a reliable approach for the fast diagnosis and early identification of sepsis.

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