Fu Yuanji, Bonifacio-Mundaca Jenny, Desterke Christophe, Casafont Íñigo, Mata-Garrido Jorge
Institut Necker Enfants Malades, INSERM, CNRS, Université Paris Cité, F-75015 Paris, France.
National Tumor Bank, Department of Pathology, National Institute of Neoplastic Diseases, Surquillo 15038, Peru.
Genes (Basel). 2025 Jul 30;16(8):920. doi: 10.3390/genes16080920.
Hepatic cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are major global health concerns due to rising incidence and limited therapeutic success. While traditional risk factors include chronic liver disease and environmental exposures, recent evidence underscores the significance of genetic alterations and gut microbiota in liver cancer development and progression. This review aims to integrate emerging knowledge on the interplay between host genomic changes and gut microbial dynamics in the pathogenesis and treatment of hepatic cancers. We conducted a comprehensive review of current literature on genetic and epigenetic drivers of HCC and CCA, focusing on commonly mutated genes such as , , , , and . In parallel, we evaluated studies addressing the gut-liver axis, including the roles of dysbiosis, microbial metabolites, and immune modulation. Key clinical and preclinical findings were synthesized to explore how host-microbe interactions influence tumorigenesis and therapeutic response. HCC and CCA exhibit distinct but overlapping genomic landscapes marked by recurrent mutations and epigenetic reprogramming. Alterations in the gut microbiota contribute to hepatic inflammation, genomic instability, and immune evasion, potentially enhancing oncogenic signaling pathways. Furthermore, microbiota composition appears to affect responses to immune checkpoint inhibitors. Emerging therapeutic strategies such as probiotics, fecal microbiota transplantation, and precision oncology based on mutational profiling demonstrate potential for personalized interventions. The integration of host genomics with microbial ecology provides a promising paradigm for advancing diagnostics and therapies in liver cancer. Targeting the gut-liver axis may complement genome-informed strategies to improve outcomes for patients with HCC and CCA.
肝癌，包括肝细胞癌（HCC）和胆管癌（CCA），由于发病率上升和治疗效果有限，已成为全球主要的健康问题。虽然传统的风险因素包括慢性肝病和环境暴露，但最近的证据强调了基因改变和肠道微生物群在肝癌发生和发展中的重要性。本综述旨在整合关于宿主基因组变化与肠道微生物动态之间相互作用在肝癌发病机制和治疗中的新认识。我们对目前关于HCC和CCA的遗传和表观遗传驱动因素的文献进行了全面综述，重点关注常见的突变基因，如 、 、 、 和 。同时，我们评估了涉及肠-肝轴的研究，包括生态失调、微生物代谢产物和免疫调节的作用。综合关键的临床和临床前研究结果，以探讨宿主-微生物相互作用如何影响肿瘤发生和治疗反应。HCC和CCA表现出独特但重叠的基因组格局，其特征是反复突变和表观遗传重编程。肠道微生物群的改变会导致肝脏炎症、基因组不稳定和免疫逃逸，可能增强致癌信号通路。此外，微生物群组成似乎会影响对免疫检查点抑制剂的反应。新兴的治疗策略，如益生菌、粪便微生物群移植和基于突变谱分析的精准肿瘤学，显示出个性化干预的潜力。将宿主基因组学与微生物生态学相结合，为推进肝癌的诊断和治疗提供了一个有前景的范例。针对肠-肝轴可能补充基于基因组信息的策略，以改善HCC和CCA患者的治疗效果。
