Background: We aimed to determine the significance of Porphyromonas gingivalis (P. gingivalis) in promoting tumour progression in the tumour microenvironment (TME) of oral squamous cell carcinoma (OSCC).
Methods: The Gene Expression Omnibus (GEO) was used to screen out the differentially expressed genes from the two datasets of GEO138206 and GSE87539. Immunohistochemistry and immunofluorescence analysis of samples, cell biological behaviour experiments, and tumour-bearing animal experiments were used to verify the results in vivo and in vitro. The mechanism was revealed at the molecular level, and rescue experiments were carried out by using inhibitors and lentiviruses.
Results: CXCL2 was selected by bioinformatics analysis and was found to be related to a poor prognosis in OSCC patients. Samples with P. gingivalis infection in the TME of OSCC had the strongest cell invasion and proliferation and the largest tumour volume in tumour-bearing animal experiments and exhibited JAK1/STAT3 signalling pathway activation and epithelial-mesenchymal transition (EMT). The expression of P. gingivalis, CXCL2 and TANs were independent risk factors for poor prognosis in OSCC patients. A CXCL2/CXCR2 signalling axis inhibitor significantly decreased the invasion and proliferation ability of cells and the tumour volume in mice. When lentivirus was used to block the CXCL2/CXCR2 signalling axis, the activity of the JAK1/STAT3 signalling pathway was decreased, and the phenotype of EMT was reversed.
Conclusion: Porphyromonas gingivalis promotes OSCC progression by recruiting TANs via activation of the CXCL2/CXCR2 axis in the TME of OSCC.
Keywords: Chemokine; EMT; Oral squamous cell carcinoma; Periodontal disease; Porphyromonas gingivalis; Prognosis.
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.