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摘要: 炎症性肠病(inflammatory bowel disease，IBD)包括溃疡性结肠炎(ulcerative colitis，UC)的发病率在我国呈逐渐升高的趋势。随着诊治水平的进展，长病程的UC患者逐渐增多，发生结直肠癌(colorectal cancer，CRC)的风险明显增加。UC癌变的危险因素主要包括长病程、广泛肠段受累、累积炎症负担(cumulative inflammatory burden，CIB)、合并原发性硬化性胆管炎(primary sclerosing cholangitis，PSC)、CRC家族史等，其中炎症的反复发作是癌变的独立危险因素。结肠炎相关结直肠癌(colitis-associated colorectal cancer, CAC)与散发性CRC在癌变模式、发生机制、分子特征等方面均存在差异。本文将结合近年来的研究进展，详细阐述遗传和表观遗传的改变、氧化应激、异常免疫反应以及肠道菌群失调在炎癌转化中发挥的作用。基于危险因素对UC患者进行CAC风险分层，高危患者应进行更频繁的结肠镜监测以便早发现、早干预、早治疗。Abstract: The incidence of inflammatory bowel disease(IBD), including ulcerative colitis(UC), is gradually rising in China. With the progress of diagnosis and treatment, the number of UC patients with a long-term course of the disease is increasing, and their risk of developing colorectal cancer(CRC) is significantly increased. Risk factors for UC carcinogenesis include long-term course of the disease, extensive intestinal involvement, cumulative inflammatory burden(CIB), primary sclerosing cholangitis(PSC), and family history of CRC, among which recurrent inflammation is an independent risk factor for cancerogenesis. Colitis-associated colorectal cancer(CAC) and sporadic colorectal cancer are different in terms of carcinogenesis pattern, pathogenesis, and molecular characteristics. In this article, we will discuss the role of genetic and epigenetic changes, oxidative stress, abnormal immune response and intestinal flora disorder in the transformation from colitis to carcinoma. The risk stratification of CAC was performed for UC patients based on these risk factors. High-risk patients should undergo more frequent surveillance through colonoscopy for early detection, intervention, and treatment.
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表 1 CAC和sCRC的异同
项目 CAC sCRC 危险因素 广泛肠段受累、长病程、组织学炎症、CIB、合并PSC、CRC家族史等 年龄、环境因素(如吸烟、饮酒)、遗传因素等 起源 异型增生，形态更平坦，弥漫性，局灶或多灶 腺瘤(和无蒂锯齿状息肉)，病灶离散 癌变模式 慢性炎症-不确定性异型增生-低级别异型增生-高级别异型增生-癌，“大爆炸”模型 早期腺瘤-中期腺瘤-晚期腺瘤-癌，“随机”模型 发生机制 遗传和表观遗传改变，氧化应激，异常免疫反应，肠道菌群失调 CIN、MSI、CIMP 基因突变 早期p53突变，且频率较高；晚期APC突变，且频率较低 早期APC突变，晚期p53突变 共识分子亚型 典型上皮型(CMS2)为主 间叶型(CMS4)为主 分子特征 表现出上皮分化特征和显著的Wnt和MYC信号激活 常有上皮-间充质转化(epithelial-mesenchymal transformation，EMT)相关基因的上调，TGF-β激活，间质浸润和血管生成 预后 较好 较差 
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| 引用本文: |
李沐涵, 李景南. 溃疡性结肠炎癌变相关机制研究进展[J]. 中国中西医结合消化杂志, 2023, 31(4): 243-249. doi: 10.3969/j.issn.1671-038X.2023.04.02
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| Citation: |
LI Muhan, LI Jingnan. Advances on the pathogenesis of cancerogenesis in ulcerative colitis[J]. Chin J Integr Tradit West Med Dig, 2023, 31(4): 243-249. doi: 10.3969/j.issn.1671-038X.2023.04.02
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