Mohamed Sara H, Hamed Mohamed, Alamoudi Hussain A, Jastaniah Zayd, Alakwaa Fadhl M, Reda Asmaa
Department of Microbiology, Egyptian Drug Authority (EDA), formerly National Organization for Drug Control and Research (NODCAR), Giza 14281, Egypt.
Institute for Biostatistics and Informatics in Medicine and Ageing Research (IBIMA), Rostock University Medical Center, Rostock 18057, Germany.
Brief Bioinform. 2025 May 1;26(3). doi: 10.1093/bib/bbaf241.
Helicobacter pylori infection is one of the most common gastric pathogens; however, the molecular mechanisms driving its progression to gastric cancer remain poorly understood. This study aimed to identify the key transcriptomic drivers and therapeutic targets of H. pylori-associated gastric cancer through an integrative transcriptomic analysis. This analysis integrates microarray and RNA-seq datasets to identify significant differentially expressed genes (DEGs) involved in the progression of H. pylori-associated gastric cancer. In addition to independent analyses, data were integrated using ComBat to detect consistent expression patterns of hub genes. This approach revealed distinct clustering patterns and stage-specific transcriptional changes in common DEGs across disease progression, including H. pylori infection, gastritis, atrophy, and gastric cancer. Genes such as TPX2, MKI67, EXO1, and CTHRC1 exhibited progressive upregulation from infection to cancer, highlighting involvement in cell cycle regulation, DNA repair, and extracellular matrix remodeling. These findings provide insights into molecular shifts linking inflammation-driven infection to malignancy. Furthermore, network analysis identified hub genes, including CXCL1, CCL20, IL12B, and STAT4, which are enriched in immune pathways such as chemotaxis, leukocyte migration, and cytokine signaling. This emphasizes their role in immune dysregulation and tumor development. Expression profiling demonstrated the upregulation of hub genes in gastric cancer and stage-specific changes correlating with disease progression. Finally, drug-gene interaction analysis identified therapeutic opportunities, with hub genes interacting with approved drugs like abatacept and zoledronic acid, as well as developmental drugs such as adjuvant and relapladib. These findings highlight the key role of these hub genes as biomarkers and therapeutic targets, providing a foundation for advancing precision medicine in H. pylori-associated gastric cancer. Overall, this study paves the way for advancing precision medicine in H. pylori-associated gastric cancer by providing insights into the development of early detection biomarkers, risk stratification, and targeted therapies. This supports the clinical translation of precision medicine strategies in H. pylori-associated gastric cancer.
幽门螺杆菌感染是最常见的胃部病原体之一；然而，驱动其发展为胃癌的分子机制仍知之甚少。本研究旨在通过综合转录组分析确定幽门螺杆菌相关胃癌的关键转录组驱动因素和治疗靶点。该分析整合了微阵列和RNA测序数据集，以识别参与幽门螺杆菌相关胃癌进展的显著差异表达基因（DEG）。除了独立分析外，还使用ComBat整合数据以检测枢纽基因的一致表达模式。这种方法揭示了疾病进展过程中常见DEG的不同聚类模式和阶段特异性转录变化，包括幽门螺杆菌感染、胃炎、萎缩和胃癌。TPX2、MKI67、EXO1和CTHRC1等基因从感染到癌症呈现出渐进性上调，突出了它们在细胞周期调控、DNA修复和细胞外基质重塑中的作用。这些发现为将炎症驱动的感染与恶性肿瘤联系起来的分子变化提供了见解。此外，网络分析确定了枢纽基因，包括CXCL1、CCL20、IL12B和STAT4，它们在趋化作用、白细胞迁移和细胞因子信号传导等免疫途径中富集。这强调了它们在免疫失调和肿瘤发展中的作用。表达谱分析表明枢纽基因在胃癌中上调，且与疾病进展相关的阶段特异性变化。最后，药物-基因相互作用分析确定了治疗机会，枢纽基因与阿巴西普和唑来膦酸等已批准药物以及佐剂和瑞普拉地布等开发中的药物相互作用。这些发现突出了这些枢纽基因作为生物标志物和治疗靶点的关键作用，为推进幽门螺杆菌相关胃癌的精准医学奠定了基础。总体而言，本研究通过深入了解早期检测生物标志物的开发、风险分层和靶向治疗，为推进幽门螺杆菌相关胃癌的精准医学铺平了道路。这支持了幽门螺杆菌相关胃癌精准医学策略的临床转化。
