Purpose

Increasing evidence indicates that the microbiome may influence tumor growth and modulate the tumor microenvironment of gastrointestinal cancers. However, the role of oral bacteria in the development of esophageal squamous cell carcinoma (EsoSCC) has remained unclear. Herein, we investigated the relationship between the periodontal pathogen Porphyromonas gingivalis and EsoSCC.

Methods

To identify bacterial biomarkers associated with EsoSCC, we analyzed microbiomes in oral biofilms. The presence of P. gingivalis in esophageal tissues and relationships of P. gingivalis infection with clinicopathologic characteristics in 156 patients with EsoSCC were assessed using immunohistochemistry. The role of P. gingivalis infection in in vitro and in vivo EsoSCC progression was also assessed.

Results

Microbiota profiles in oral biofilms revealed that P. gingivalis abundance was associated with an increased risk of EsoSCC development. In total, 57% of patients with EsoSCC were found to be infected with P. gingivalis. The presence of P. gingivalis was found to be associated with advanced clinical stages and a poor prognosis. It was also found to be associated with an elevated esophageal cancer incidence in a 4-nitroquinoline 1-oxide-induced mouse model and with an increased xenograft tumor growth. P. gingivalis infection increased interleukin (IL)‐6 production and it promoted epithelial-mesenchymal transition and the recruitment of myeloid-derived suppressor cells. Furthermore, inhibited IL‐6 signaling attenuated the tumor-promoting effects of P. gingivalis in 4-nitroquinoline 1-oxide-treated mice and xenograft mouse models.

Conclusions

Our data indicate that P. gingivalis may promote esophageal cancer development and progression. Direct targeting of P. gingivalis or concomitant IL-6 signaling may be a promising strategy to prevent and/or treat EsoSCC associated with P. gingivalis infection.

中文翻译：

---

牙龈卟啉单胞菌促进食管鳞状细胞癌的肿瘤进展

 目的

越来越多的证据表明，微生物组可能影响肿瘤生长并调节胃肠道癌症的肿瘤微环境。然而，口腔细菌在食管鳞状细胞癌（EsoSCC）发展中的作用仍不清楚。在此，我们研究了牙周病原菌牙龈卟啉单胞菌与 EsoSCC 之间的关系。

 方法

为了识别与 EsoSCC 相关的细菌生物标志物，我们分析了口腔生物膜中的微生物组。使用免疫组织化学方法评估 156 例 EsoSCC 患者食管组织中牙龈卟啉单胞菌的存在以及牙龈卟啉单胞菌感染与临床病理特征的关系。还评估了牙龈卟啉单胞菌感染在体外和体内EsoSCC 进展中的作用。

 结果

口腔生物膜中的微生物群谱显示，牙龈卟啉单胞菌丰度与 EsoSCC 发展风险增加相关。总共有 57% 的 EsoSCC 患者被发现感染牙龈卟啉单胞菌。研究发现牙龈卟啉单胞菌的存在与晚期临床分期和不良预后相关。还发现它与 4-硝基喹啉 1-氧化物诱导的小鼠模型中食道癌发病率升高以及异种移植肿瘤生长增加有关。牙龈卟啉单胞菌感染增加白细胞介素 (IL)-6 的产生，促进上皮间质转化和骨髓源性抑制细胞的募集。此外，在 4-硝基喹啉 1-氧化物处理的小鼠和异种移植小鼠模型中，抑制 IL-6 信号传导减弱了牙龈卟啉单胞菌的促肿瘤作用。

 结论

我们的数据表明牙龈卟啉单胞菌可能促进食管癌的发生和进展。直接靶向牙龈卟啉单胞菌或伴随的 IL-6 信号传导可能是预防和/或治疗与牙龈卟啉单胞菌感染相关的 EsoSCC 的有前途的策略。