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Porphyromonas gingivalis Activation of Tumor-Associated Macrophages via DOK3 Promotes Recurrence of Oral Squamous Cell Carcinoma

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, characterized by high recurrence rate resulting in poor prognosis. Porphyromonas gingivalis, most closely correlated with chronic periodontitis, is increasingly thought to play a significant role in OSCC dev...

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Autores principales: Li, Chen-xi, Su, Ying, Gong, Zhong-cheng, Liu, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Scientific Literature, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562789/
https://www.ncbi.nlm.nih.gov/pubmed/36210538
http://dx.doi.org/10.12659/MSM.937126
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author Li, Chen-xi
Su, Ying
Gong, Zhong-cheng
Liu, Hui
author_facet Li, Chen-xi
Su, Ying
Gong, Zhong-cheng
Liu, Hui
author_sort Li, Chen-xi
collection PubMed
description BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, characterized by high recurrence rate resulting in poor prognosis. 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/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.
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spelling pubmed-95627892022-10-27 Porphyromonas gingivalis Activation of Tumor-Associated Macrophages via DOK3 Promotes Recurrence of Oral Squamous Cell Carcinoma Li, Chen-xi Su, Ying Gong, Zhong-cheng Liu, Hui Med Sci Monit Database Analysis BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy, characterized by high recurrence rate resulting in poor prognosis. 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/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. International Scientific Literature, Inc. 2022-10-10 /pmc/articles/PMC9562789/ /pubmed/36210538 http://dx.doi.org/10.12659/MSM.937126 Text en © Med Sci Monit, 2022 https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) )
spellingShingle Database Analysis
Li, Chen-xi
Su, Ying
Gong, Zhong-cheng
Liu, Hui
Porphyromonas gingivalis Activation of Tumor-Associated Macrophages via DOK3 Promotes Recurrence of Oral Squamous Cell Carcinoma
title Porphyromonas gingivalis Activation of Tumor-Associated Macrophages via DOK3 Promotes Recurrence of Oral Squamous Cell Carcinoma
title_full Porphyromonas gingivalis Activation of Tumor-Associated Macrophages via DOK3 Promotes Recurrence of Oral Squamous Cell Carcinoma
title_fullStr Porphyromonas gingivalis Activation of Tumor-Associated Macrophages via DOK3 Promotes Recurrence of Oral Squamous Cell Carcinoma
title_full_unstemmed Porphyromonas gingivalis Activation of Tumor-Associated Macrophages via DOK3 Promotes Recurrence of Oral Squamous Cell Carcinoma
title_short Porphyromonas gingivalis Activation of Tumor-Associated Macrophages via DOK3 Promotes Recurrence of Oral Squamous Cell Carcinoma
title_sort porphyromonas gingivalis activation of tumor-associated macrophages via dok3 promotes recurrence of oral squamous cell carcinoma
topic Database Analysis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562789/
https://www.ncbi.nlm.nih.gov/pubmed/36210538
http://dx.doi.org/10.12659/MSM.937126
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