研究动态
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具核梭杆菌的存在与患者生存以及食管胃交界处和胃癌中的酸性环境有关。

Presence of Fusobacterium nucleatum in relation to patient survival and an acidic environment in oesophagogastric junction and gastric cancers.

发表日期:2024 Jul 12
作者: Yoshihiro Hara, Yoshifumi Baba, Eri Oda, Kazuto Harada, Kohei Yamashita, Tasuku Toihata, Keisuke Kosumi, Masaaki Iwatsuki, Yuji Miyamoto, Hiroyasu Tsutsuki, Qiong Gan, Rebecca E Waters, Yoshihiro Komohara, Tomohiro Sawa, Jaffer A Ajani, Hideo Baba
来源: BRITISH JOURNAL OF CANCER

摘要:

具核梭杆菌栖息于口腔并影响胃肠癌的进展。我们之前的研究结果表明具核梭菌通过 NF-κB 通路与食管鳞状细胞癌的不良预后相关。然而,其在食管胃交界处和胃腺癌中的作用仍未被探索。我们研究了具核梭菌是否影响这些癌症,并强调了其潜在影响。对两组 EGJ 和胃腺癌患者(438 名来自日本,380 名来自美国)进行了研究。通过 qPCR、FISH 和染色证实具核梭杆菌的存在。根据具核梭菌阳性率评估患者总生存期 (OS)。将 EGJ 和胃腺癌细胞系暴露于具核梭杆菌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 显着缩短。在酸性更强的肿瘤环境中,具核梭杆菌阳性率降低。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,具核梭杆菌和已知危险因素幽门螺杆菌同时出现的情况很少见。 nucleatum 可在 EGJ 和胃腺癌中诱导 NF-κB 通路,导致肿瘤进展和预后不良。© 2024。作者,获得 Springer Nature Limited 的独家许可。
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.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.