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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

Paper

complete

Experiment

complete

Data

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Analysis

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Execution

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title
Porphyromonas gingivalis Activation of Tumor-Associated Macrophages via DOK3 Promotes Recurrence of Oral Squamous Cell Carcinoma.
doi
10.12659/MSM.937126
pmid
36210538
authors array · 4 items
[0]
Chen-Xi Li
[1]
Ying Su
[2]
Zhong-Cheng Gong
[3]
Hui Liu
journal
Medical science monitor : international medical journal of experimental and clinical research
year
2022
abstract
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 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.
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The intersection of the differentially-expressed genes identified 106 commonly upregulated genes and 131 commonly downregulated genes.
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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).
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Expression data from human macrophages treated with Porphyromonas gingivalis and its components
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Genetic expression of stage IV oral squamous cell carcinoma according to the recurrence
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ct the expression of DOK3 in OSCC specimens, immunohistochemical (ICH) assay was used. RESULTS A total of 106
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36210538", "kind": "science-record", "revision": 5, "content_hash": "sha256:6ec262de8c239fa30e02c19fdc191021d8f7fcbe29500fa6de489053f17a91a5", "created_at": "2026-11-01T18:15:31Z", "updated_at": "2026-11-01T22:50:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Porphyromonas gingivalis Activation of Tumor-Associated Macrophages via DOK3 Promotes Recurrence of Oral Squamous Cell Carcinoma.", "doi": "10.12659/MSM.937126", "pmid": "36210538", "authors": ["Chen-Xi Li", "Ying Su", "Zhong-Cheng Gong", "Hui Liu"], "journal": "Medical science monitor : international medical journal of experimental and clinical research", "year": 2022, "abstract": "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 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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"structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The raw data supporting the conclusions of this article will be made available by the authors upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM612262", "GSM612263", "GSM612264", "GSM612265", "GSM612266", "GSM612267", "GSM612268", "GSM612269", "GSM612270", "GSM612271", "GSM612272", "GSM612273"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data from human macrophages treated with Porphyromonas gingivalis and its components", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE87593", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": 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"title": "Genetic expression of stage IV oral squamous cell carcinoma according to the recurrence", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE24897 not downloaded", "asset:data:geo:GSE24897 licence not read", "asset:data:geo:GSE87593 not downloaded", "asset:data:geo:GSE87593 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The 2 datasets were separately analyzed using the Limma package in R software version 4.0.2 (R Foundation for 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE24897", "GSE87593"], "resolved_accessions": ["GSE24897", "GSE87593"], "statements": ["The raw data supporting the conclusions of this article will be made available by the authors upon reasonable request."], "basis": "The paper names GSE24897, GSE87593 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:36210538", "data:geo:GSE24897"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE24897"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:08:41Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 7776, "completion_tokens": 1795, "cached_tokens": 0}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:36210538", "type": "paper", "label": "pmid:36210538"}, {"id": "source:pmid:36210538", "type": "manuscript", "label": "PMID 36210538 full text"}, {"id": "data:geo:GSE24897", "type": "dataset", "label": "GEO GSE24897"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36210538", "type": "paper", "label": "pmid:36210538"}, {"id": "source:pmid:36210538", "type": "manuscript", "label": "PMID 36210538 full text"}, {"id": "data:geo:GSE24897", "type": "dataset", "label": "GEO GSE24897"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36210538", "type": "extraction", "used": ["source:pmid:36210538"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE24897", "type": "accession_resolution", "used": ["data:geo:GSE24897"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:36210538", "parent_hash": "sha256:1823d9f6df672205d9778d2f66c5e802f75f2b22c9fef19d5202b7e79f66e83d", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE24897 licence not read", "asset:data:geo:GSE24897 not downloaded", "asset:data:geo:GSE87593 licence not read", "asset:data:geo:GSE87593 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ct the expression of DOK3 in OSCC specimens, immunohistochemical (ICH) assay was used. RESULTS A total of 106", "pression of DOK3 in 2 groups was detected by immunohistochemistry (ICH), and the results showed that the DOK3"], "order_basis": "paper_text_order:1327", "id": "assay:1"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The 2 datasets were separately analyzed using the Limma package in R software version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria)."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}