Porphyromonas gingivalis infection exacerbates oesophageal cancer and promotes resistance to neoadjuvant chemotherapy

Br J Cancer. 2021 Aug;125(3):433-444. doi: 10.1038/s41416-021-01419-5. Epub 2021 May 12.

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 (n = 85) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteroidaceae Infections / epidemiology*
  • Bacteroidaceae Infections / mortality
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chemotherapy, Adjuvant
  • Drug Resistance, Neoplasm*
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / microbiology
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / drug therapy*
  • Esophageal Squamous Cell Carcinoma / microbiology
  • Esophageal Squamous Cell Carcinoma / pathology
  • Female
  • Humans
  • Male
  • Mice
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Porphyromonas gingivalis / pathogenicity*
  • Prognosis
  • Retrospective Studies
  • Survival Analysis
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Xenograft Model Antitumor Assays