P. gingivalis Infection Promotes Resistance To Chemotherapy and Aggravates Esophageal Cancer

Objectives: To assess the effects of P. gingivalis infection on chemotherapy efficacy and prognosis of ESCC patients, and examine P. gingivalis infection-induced apoptosis resistance and acceleration of proliferation in vitro and in vivo, and its influences on the composition of esophagus microbiome
Methods: A retrospective study was conducted on 279 ESCC patients based on the computerized tomography (CT) imaging results, longitudinal cancerous tissue samples, and clinicopathologic databases, which were collected from ESCC patients prior to- and post-chemotherapy between 2010 to 2015 from the First Affiliated Hospital of HAUST. The effects of P. gingivalis infection on tumor response were evaluated according to the RECIST v.1.1. Esophageal microbiome composition, the influences of P. gingivalis infection on cell proliferation, and chemotherapy-induced apoptosis were examined in ESCC patients and validated in cultured cancer cell lines and mice model. Univariable, multivariable Cox proportional hazards regression, and ANOVA were employed to analyze the results of OS and apoptosis, respectively.
Results: P. gingivalis infection significantly reduces the response of ESCC to NACT (40.0% vs 66.7% with PR/CR; P=0.014) and exacerbates the prognosis of ESCC patients (39.3months vs 53.2months; P<0.001). The clinicopathological analysis shows that the percentage of P. gingivalis infection is statistically higher in patients with severer lymph node metastasis, invasion depth, and advanced TNM stage. Moreover, P. gingivalis colonization is associated with a distinct alteration of esophageal microbiome. In addition, P. infection promotes ESCC cell proliferation and leads to apoptosis resistance to chemotherapy drugs in longitudinal cancerous tissue samples from ESCC patients (P<0.001), which was also confirmed in various cultured ESCC cells and xenograft tumor-bearing mice model.
Conclusions: This is the first demonstration that P. gingivalis infection reduces chemotherapy efficacy, worsens the prognosis of ESCC, potentiates the aggressive behavior of ESCC cells, and alters the composition of esophageal microbiome, suggesting eradication of P. gingivalis could potentially enhance chemosensitivity and improve the prognosis and clinical management of ESCC.