Abstract
Background
The effect of Porphyromonas gingivalis (Pg) infection on oesophageal squamous cell carcinoma (ESCC) prognosis, chemotherapeutic efficacy, and oesophageal cancer cell apoptosis resistance and proliferation remain poorly understood.
Methods
Clinicopathological data from 312 ESCC oesophagectomy patients, along with the computed tomography imaging results and longitudinal cancerous tissue samples from a patient subset (nā=ā85) who received neoadjuvant chemotherapy (NACT), were analysed. Comparison of overall survival and response rate to NACT between Pg-infected and Pg-uninfected patients was made by multivariate Cox analysis and Response Evaluation Criteria in Solid Tumours v.1.1 criteria. The influence of Pg on cell proliferation and drug-induced apoptosis was examined in ESCC patients and validated in vitro and in vivo.
Results
The 5-year overall survival was lower in Pg-positive patients, and infection was associated with multiple clinicopathological factors and pathologic tumour, node, metastasis stage. Of the 85 patients who received NACT, Pg infection was associated with a lower response rate and 5-year overall survival. Infection with Pg resulted in apoptosis resistance in ESCC and promoted ESCC cell viability, which was confirmed in longitudinal cancerous tissue samples. Pg-induced apoptosis resistance was dependent on fimbriae and STAT3.
Conclusions
Pg infection is associated with a worse ESCC prognosis, reduced chemotherapy efficacy, and can potentiate the aggressive behaviour of ESCC cells.
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Acknowledgements
We acknowledge Drs. Mi and Zhang for assisting in the pathological evaluation and for other technical advice.
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H.W., S.G., and F.Z conceived the study. Y.L., K.L., X.D., M.M., Z.G., L.Y., and J.R. performed most of the experiments and interpreted the data. X.Y., S.L., D.A.S., R.J.L., and H.W. directed the study and supervised the research. Y.L. and K.L. collected tumour specimens and analysed the clinical data of patients. X.D., J.R., and Z.G. performed all immunofluorescence staining. Y.L. performed animal experiments. S.G., F.Z., and H.W. confirmed the histopathological findings and interpreted the clinical data. H.W. prepared the manuscript. D.A.S. and R.J.L. reviewed and edited the manuscript. All authors read and approved the final manuscript.
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Tissue samples and clinicopathological data were obtained from The First Affiliated Hospital of Henan University of Science and Technology and Anyang Peopleās Hospital. The research was approved by the Research Ethics Committee of Henan University of Science and Technology and was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent from each patient was achieved. All animal experiments were authorised through the Animal Care and Use Committee of Henan University of Science and Technology (HAUST). All animal experiments were conducted in accordance with the Guidelines for Animal Health and Use of Henan University of Science and Technology (HAUST).
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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The authors declare no competing interests.
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This research was supported by grants DE026727 (H.W.), DE017921, DE011111 (R.J.L.), and DE017680 (D.A.S.) from National Institute of Dental and Craniofacial Research, NIH, USA, and by the Natural Science Foundation of China (NSFC, GS 81472234), and Key Programs of Science and Technology of Henan Province (KPST-HN, GS 161100311200).
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Gao, S., Liu, Y., Duan, X. et al. Porphyromonas gingivalis infection exacerbates oesophageal cancer and promotes resistance to neoadjuvant chemotherapy. Br J Cancer 125, 433ā444 (2021). https://doi.org/10.1038/s41416-021-01419-5
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DOI: https://doi.org/10.1038/s41416-021-01419-5
