Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Division of Translational Research and Advanced Treatment Against Gastrointestinal Cancer, Kumamoto University, 1-1-1 Honjo, Chuoku, Kumamoto, 860-8556, Japan.
Br J Cancer. 2024 Sep;131(5):797-807. doi: 10.1038/s41416-024-02753-0. Epub 2024 Jul 12.
Fusobacterium nucleatum inhabits the oral cavity and affects the progression of gastrointestinal cancer. Our prior findings link F. nucleatum to poor prognosis in oesophageal squamous cell carcinoma via NF-κB pathway. However, its role in oesophagogastric junction and gastric adenocarcinoma remains unexplored. We investigated whether F. nucleatum influences these cancers, highlighting its potential impact.
Two cohorts of EGJ and gastric adenocarcinoma patients (438 from Japan, 380 from the USA) were studied. F. nucleatum presence was confirmed by qPCR, FISH, and staining. Patient overall survival (OS) was assessed based on F. nucleatum positivity. EGJ and gastric adenocarcinoma cell lines were exposed to F. nucleatum to study molecular and phenotypic effects, validated in xenograft mouse model.
In both cohorts, F. nucleatum-positive EGJ or gastric adenocarcinoma patients had notably shorter OS. F. nucleatum positivity decreased in more acidic tumour environments. Cancer cell lines with F. nucleatum showed enhanced proliferation and NF-κB activation. The xenograft model indicated increased tumour growth and NF-κB activation in F. nucleatum-treated cells. Interestingly, co-occurrence of F. nucleatum and Helicobacter pylori, a known risk factor, was rare.
F. nucleatum can induce the NF-κB pathway in EGJ and gastric adenocarcinomas, leading to tumour progression and poor prognosis.
具核梭杆菌栖息于口腔内，并影响胃肠道癌症的进展。我们先前的研究结果表明，具核梭杆菌通过 NF-κB 通路与食管鳞状细胞癌的不良预后相关。然而，其在食管胃交界部和胃腺癌中的作用尚未被探索。我们研究了具核梭杆菌是否会影响这些癌症，并强调了其潜在的影响。
研究了两个队列的 EGJ 和胃腺癌患者（日本 438 例，美国 380 例）。通过 qPCR、FISH 和染色来确认具核梭杆菌的存在。根据具核梭杆菌阳性评估患者的总生存（OS）。将 EGJ 和胃腺癌细胞系暴露于具核梭杆菌中，以研究分子和表型效应，并在异种移植小鼠模型中进行验证。
在两个队列中，具核梭杆菌阳性的 EGJ 或胃腺癌患者的 OS 明显缩短。在酸性肿瘤环境中，具核梭杆菌的阳性率降低。具有具核梭杆菌的癌细胞系显示出增强的增殖和 NF-κB 激活。异种移植模型表明，具核梭杆菌处理的细胞中肿瘤生长和 NF-κB 激活增加。有趣的是，具核梭杆菌和已知风险因素幽门螺杆菌的共同存在很少见。
具核梭杆菌可诱导 EGJ 和胃腺癌中的 NF-κB 通路，导致肿瘤进展和不良预后。
