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. 2022 Jul 26:16:936955.
doi: 10.3389/fnint.2022.936955. eCollection 2022.

B serum proteome profiles revealed dysregulated proteins and mechanisms associated with insomnia patients: A preliminary study

Tao Liu  1   2 , Guanying Wang  3 , Xingping Zhang  1   4 , Xin Liu  4 , Zhengting Liang  4 , Xiaojuan Ren  5 , Deqi Yan  4 , Wenhui Zhang  4
Affiliations

B serum proteome profiles revealed dysregulated proteins and mechanisms associated with insomnia patients: A preliminary study

Tao Liu et al. Front Integr Neurosci. .

Abstract

Background: Insomnia is a clinical problem of significant public health importance; however, the underlying pathogenesis of this disorder is not comprehensively understood.

Methods: To identify potential treatment targets and unfold one of the gaps that were involved in insomnia pathological mechanisms, we employed a tandem mass tag-based (TMT) quantitative proteomics technology to detect differentially expressed proteins (DEPs) in serum from patients with insomnia and controls. DEPs were further analyzed by bioinformatics platforms. In addition, parallel reaction monitoring (PRM) was used to verify the TMT results.

Results: Patients with insomnia had poorer sleep quality compared with healthy controls. A total of 106 DEPs were identified among patients with insomnia and controls. They were mainly enriched in immune and inflammation-related biological functions and signaling pathways. Using the protein-protein interaction network, we screened the 10 most connected proteins as key DEPs. We predicted that four key DEPs were subject to targeted regulation by natural compounds of herbs. Eight key DEPs were validated using PRM in an additional 15 patients with insomnia and 15 controls, and the results also supported the experimental findings.

Conclusion: We identified aberrantly expressed proteins in insomnia that may be involved in the immune-inflammatory response. The 10 key DEPs screened may be potential targets for insomnia, especially FN1, EGF, HP, and IGF1. The results of this study will broaden our understanding of the pathological mechanisms of insomnia and provide more possibilities for pharmacotherapy.

Keywords: PRM; immuno-inflammation; insomnia; protein expression; sleep.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The flowchart of this study. GO, Gene Ontology; GSEA, gene set enrichment analysis; KEGG, Kyoto Encyclopedia of Genes and Genomes; PPI, protein–protein interaction; PRM, parallel reaction monitoring; PSG, polysomnography; PSQI, Pittsburgh Sleep Quality Index.
FIGURE 2
FIGURE 2
Identification of differentially expressed proteins between insomnia patients and controls. (A) Heatmap clustered with unsupervised for differentially expressed proteins between patients with insomnia and controls. F1-3 and G1-3 refer to technical replicates. (B) Volcano plot of differentially expressed proteins between patients with insomnia and controls. Red is upregulated proteins and blue is downregulated. G, insomnia group; F, control group.
FIGURE 3
FIGURE 3
Identification of GO and signaling pathways enriched by differentially expressed proteins. (A) Top 10 terms of BP, CC, and MF enriched in insomnia patients. (B) KEGG pathways of DEPs significantly enriched. (C) Heatmap clustered with unsupervised for the activated or inhibited KEGG pathways were calculated by GSVA. (D) The significant hallmark terms positively corrected with patients with insomnia. G, insomnia group; F, control group.
FIGURE 4
FIGURE 4
Identification of key proteins involved in insomnia. (A) The PPI network of DEPs. Nodes are colored from blue to red, indicating increased connectivity of proteins. (B) Top 10 proteins with the highest connectivity in the network. (C) Prediction network for natural compounds of herbal medicines targeting key DEPs.
FIGURE 5
FIGURE 5
The expression of key DEPs. The expression of key DEPs in insomnia patients and controls in TMT-based proteomics. *p < 0.05, **p < 0.01, ***p < 0.001.
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