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. 2022 Jun 6:2022:5672384.
doi: 10.1155/2022/5672384. eCollection 2022.

The Underlying Molecular Basis and Mechanisms of Venous Thrombosis in Patients with Osteomyelitis: A Data-Driven Analysis

Peisheng Chen  1   2   3 , Yinhuan Liu  4 , Xiaofeng Lin  5 , Bin Yu  6 , Bin Chen  1   2   3 , Fengfei Lin  1   2   3
Affiliations

The Underlying Molecular Basis and Mechanisms of Venous Thrombosis in Patients with Osteomyelitis: A Data-Driven Analysis

Peisheng Chen et al. Genet Res (Camb). .

Abstract

Objective: Osteomyelitis (OM) is one of the most risky and challenging diseases. Emerging evidence indicates OM is a risk factor for increasing incidence of venous thromboembolism (VTE) development. However, the mechanisms have not been intensively investigated.

Methods: The OM-related dataset GSE30119 and VTE-related datasets GSE19151 and GSE48000 were downloaded from the Gene Expression Omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs) (OMGs1 and VTEGs1, respectively). Functional enrichment analyses of Gene Ontology (GO) terms were performed. VTEGs2 and OMGs2 sharing the common GO biological process (GO-BP) ontology between OMGs1 and VTEGs1 were detected. The TRRUST database was used to identify the upstream transcription factors (TFs) that regulate VTEGs2 and OMGs2. The protein-protein interaction (PPI) network between VTEGs2 and OMGs2 was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and then visualized in Cytoscape. Topological properties of the PPI network were calculated by NetworkAnalyzer. The Molecular Complex Detection (MCODE) plugin was utilized to perform module analysis and choose the hub modules of the PPI network.

Results: A total of 587 OMGs1 and 382 VTEGs1 were identified from the related dataset, respectively. GO-BP terms of OMGs1 and shared DGEs1 were mainly enriched in the neutrophil-related immune response process, and the shared GO-BP terms of OMGs1 and VTEGs1 seemed to be focused on cell activation, immune, defense, and inflammatory response to stress or biotic stimulus. 230 VTEGs2, 333 OMGs2, and 13 shared DEGs2 were detected. 3 TF-target gene pairs (SP1-LSP1, SPI1-FCGR1A, and STAT1-FCGR1A) were identified. The PPI network contained 1611 interactions among 467 nodes. The top 10 hub proteins were TP53, IL4, MPO, ELANE, FOS, CD86, HP, SOCS3, ICAM1, and SNRPG. Several core nodes (such as MPO, ELANE, and CAMP) were essential components of the neutrophil extracellular traps (NETs) network.

Conclusion: This is the first data-mining study to explore shared signatures between OM and VTE by the integrated bioinformatic approach, which can help uncover potential biomarkers and therapeutic targets of OM-related VTE.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
A flowchart of the present study.
Figure 2
Figure 2
A Venn plot of OMGs1 and VTEGs1. Heart-shaped dotted line represents the shared DGEs1.
Figure 3
Figure 3
Results of the GO-BP terms enrichment analyses for (a) OMGs1, (b) VTEGs1, and (c) shared DGEs1 and (d) shared GO-BP enrichment of VTEGs1 and OMGs.
Figure 4
Figure 4
The DEGs2 enclosed by all sharing GO-BP terms. (a) A Venn plot of OMGs2 and VTEGs2. (b) PPI network of the shared DGEs2. (c) Fold change of the shared DGEs2.
Figure 5
Figure 5
Analysis of the PPI network of DEGs2. (a) PPI network of OMGs2 and VTEGs2. (b) Module 1 of the PPI network of DEGs2. (c) Module 2 of the PPI network of DEGs2. (d) Module 3 of the PPI network of DEGs2. The node sizes correspond to the degree of the node, while the node color denotes betweenness centrality.
See this image and copyright information in PMC

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