Abstract:

Ulcerative colitis-related colorectal cancer (UC-CRC) is a typical inflammation-related cancer with a unique and complex carcinogenic mechanism. Identifying its core mechanisms is of significant clinical importance for its early diagnosis and precise prevention. This review systematically summarizes the roles and research progress of chronic inflammation-driven DNA damage, characteristic genetic and epigenetic alterations, tumor microenvironment remodeling, immune evasion mechanisms, and gut microbiota dysbiosis in the carcinogenic process of ulcerative colitis. Studies have shown that UC-CRC exhibits early p53 mutations, a significant increase in microsatellite instability, and relatively delayed KRAS and APC mutations in terms of genetic characteristics. In the tumor microenvironment, its features include the activation of cancer-associated fibroblasts, angiogenesis, and abnormal expansion of cancer stem cells. Moreover, immune evasion mechanisms, such as macrophage polarization, dendritic cell dysfunction, T-cell exhaustion, etc. further promote carcinogenesis. Additionally, the abnormal colonization of pro-carcinogenic gut microbiota exacerbates chronic inflammation and immune imbalance in the host, significantly increasing the risk of malignancy. Future research directions will focus on the early identification of p53 mutations, microsatellite instability, and characteristic microbial populations, precise targeted intervention in key pathways, and the fine-tuned regulation of the gut microbiota as crucial strategies for the early diagnosis and precision treatment of UC-CRC.

Key words:

Ulcerative colitis, Colorectal cancer, Carcinogenic mechanism, Progress

摘要：

溃疡性结肠炎相关结直肠癌（ulcerative colitis-related colorectal cancer，UC-CRC）是一种典型的炎症相关癌症，其癌变机制独特且复杂，明确其核心机制对于早期诊断和精准防控具有重要临床意义。本文系统综述了慢性炎症驱动的DNA损伤、特征性遗传与表观遗传改变、肿瘤微环境重塑、免疫逃逸机制及肠道微生态失衡在溃疡性结肠炎癌变过程中的作用与研究进展。研究表明，UC-CRC在遗传学特征方面表现为p53突变早期发生、微卫星不稳定性显著增加、KRAS和APC突变相对延迟；在肿瘤微环境中则以癌相关成纤维细胞活化、血管新生和肿瘤干细胞异常扩增为特征；而巨噬细胞极化、树突状细胞功能障碍及T细胞耗竭等免疫逃逸机制则进一步促进了癌变进程。此外，肠道致癌菌群的异常定植加剧了宿主慢性炎症与免疫失衡，显著提升了癌变风险。未来针对p53突变、微卫星不稳定性及特征菌群的早期识别、关键通路的精准靶向干预以及微生态的精准调控策略，将成为UC-CRC早期诊断与精准治疗的重要研究方向。

关键词:

溃疡性结肠炎, 结直肠癌, 癌变机制, 进展