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pmid:36210538
Porphyromonas gingivalis Activation of Tumor-Associated Macrophages via DOK3 Promotes Recurrence of Oral Squamous Cell Carcinoma.
Chen-Xi Li · Ying Su · Zhong-Cheng Gong · Hui Liu
Medical science monitor : international medical journal of experimental and clinical research · 2022 doi:10.12659/MSM.937126
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Complete file
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Porphyromonas gingivalis, most closely correlated with chronic periodontitis, is increasingly thought to play a significant role in OSCC development via influencing tumor-associated macrophages. However, its specific function remains unclear. In this study, we attempted to explore the mechanism of action of P. gingivalis in the recurrence of OSCC by bioinformatics analysis, to lay a foundation for subsequent basic experiments. MATERIAL AND METHODS The P. gingivalis-infected macrophage microarray dataset (GSE24897) and the OSCC advanced relapse patient microarray dataset (GSE87593) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially-expressed genes (DEGs) were screened using R system, and the intersected DEGs were analyzed for functional enrichment, and protein-protein interaction (PPI) networks were constructed. The expression of significant DEG in GSE24897 microarray was assessed to determine its effect on macrophage immune infiltration in pan-cancer by applying the TIMER 2.0 repository. To detect the expression of DOK3 in OSCC specimens, immunohistochemical (ICH) assay was used. RESULTS A total of 106 co-expressed DEGs were upregulated and 131 were downregulation. The biological processes were mainly enriched in DNA-templated transcription terms, the cellular component enrichment was mainly enriched in the nucleus terms, and the molecular function enrichment was mainly enriched in protein-binding function terms. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the DEGs were mainly enriched in the MAPK signaling pathway. Overall analysis of the PPI network showed a significant aggregation, with the top 10 hub co-expressed genes (CASP3, FYN, HNRNPA2B1, NR3C1, RELA, REL, POLR2F, RAN, RHOA, and STAT5B). DOK3 is significantly upregulated in P. gingivalis-infected macrophages, which is associated with macrophage infiltration and differentiation. There was more positive DOK3 staining in the group with P. gingivalis infection. CONCLUSIONS P. gingivalis can affect the recurrence of OSCC by increasing the expression of DOK3 in TAMs, which may be involved in activation of signaling pathways such as TNF and MAPK.", "claims": [{"id": "claim-method", "statement": "The 2 datasets were separately analyzed using the Limma package in R software version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36210538", "locator": "sections[5] \"Differentially-Expressed Gene Analysis\" paragraph 2", "quote": "The 2 datasets were separately analyzed using the Limma package in R software version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data supporting the conclusions of this article will be made available by the authors upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36210538", "locator": "sections[23] \"fn-group\" paragraph 1", "quote": "The raw data supporting the conclusions of this article will be made available by the authors upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The intersection of the differentially-expressed genes identified 106 commonly upregulated genes and 131 commonly downregulated genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36210538", "locator": "sections[13] \"Identification of DEGs\" paragraph 2", "quote": "Posterior to taking the intersection of the 2 collections, there were 106 genes in common among all upregulated genes (Figure 2A) and 131 genes in common among all downregulated genes (Figure 2B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The intersection of the differentially-expressed genes identified 106 commonly upregulated genes and 131 commonly downregulated genes.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36210538"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE24897"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE24897"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36210538", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.12659/MSM.937126", "sha256": 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