Li Wei, Liu Tong, Wu Tianhua, Cai Ting, Wang Fen, Zhang Minglin
Department of General Surgery, Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, Guangdong, China.
Department of Gastroenterology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, 61 Jiefang Road, Changsha, Hunan 410005, China.
Biochim Biophys Acta Rev Cancer. 2025 Nov;1880(6):189492. doi: 10.1016/j.bbcan.2025.189492. Epub 2025 Nov 7.
Helicobacter pylori (H. pylori), a Group I carcinogen that affects approximately half of the global population, is the primary aetiological agent of chronic gastritis, peptic ulcers, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. Its pathogenesis involves intricate interactions among bacterial virulence factors, host genetics, and environmental factors. We detail the critical role of diverse protein posttranslational modifications (PTMs) in mediating H. pylori-induced gastric mucosal damage and carcinogenesis. We describe how H. pylori exploits and dysregulates a broad spectrum of host and bacterial PTMs (encompassing acetylation, ubiquitination, S-nitrosylation, disulfide bond formation, citrullination, methylation, glycosylation, phosphorylation, SUMOylation, and ADP-ribosylation) to establish infection, evade immune responses, drive chronic inflammation, and promote malignant transformation. Collectively, these findings reveal a complex, multilayered PTM network that is central to H. pylori pathogenesis. Understanding these mechanisms provides crucial insights for the development of novel diagnostic biomarkers; methylation profiles; anti-citrullinate keratin 1 (Cit-K1) antibodies, maps of PTM dynamics; targeted therapeutic strategies, including PTM enzyme inhibitors, antivirulence agents such as H. pylori disulfide bond-forming protein A inhibitors, epigenetic modulators, glycoconjugate vaccines/adhesion blockers, and optimized drug delivery systems such as N-acetylcysteine liposomes. Furthermore, this knowledge supports improved risk stratification for managing persistent cancer risk even after eradication.
幽门螺杆菌（H. pylori）是一种I类致癌物，全球约一半人口受其影响，它是慢性胃炎、消化性溃疡、胃腺癌和胃黏膜相关淋巴组织淋巴瘤的主要病因。其发病机制涉及细菌毒力因子、宿主遗传学和环境因素之间的复杂相互作用。我们详细阐述了多种蛋白质翻译后修饰（PTM）在介导幽门螺杆菌诱导的胃黏膜损伤和致癌作用中的关键作用。我们描述了幽门螺杆菌如何利用和失调广泛的宿主和细菌PTM（包括乙酰化、泛素化、S-亚硝基化、二硫键形成、瓜氨酸化、甲基化、糖基化、磷酸化、SUMO化和ADP-核糖基化）来建立感染、逃避免疫反应、引发慢性炎症和促进恶性转化。总的来说，这些发现揭示了一个复杂的、多层次的PTM网络，它是幽门螺杆菌发病机制的核心。了解这些机制为新型诊断生物标志物的开发提供了关键见解；甲基化谱；抗瓜氨酸化角蛋白1（Cit-K1）抗体、PTM动态图谱；靶向治疗策略，包括PTM酶抑制剂、抗毒力剂如幽门螺杆菌二硫键形成蛋白A抑制剂、表观遗传调节剂、糖缀合物疫苗/黏附阻滞剂，以及优化的药物递送系统如N-乙酰半胱氨酸脂质体。此外，这些知识有助于改善风险分层，即使在根除后也能管理持续的癌症风险。
