癌症进化发育学:基于炎-癌转化研究的新学说  

Cancer evolution-development: novel theory based on studies of inflammation-cancer transformation

作　　者：刘文斌[1] 曹广文[1] LIU Wenbin CAO Guangwen(Department of Epidemiology, Faculty of Naval Medicine, Second Military Medical Universi- ty, Shanghai 200433, Chin)

机构地区：[1]第二军医大学海军医学系流行病学教研室,上海200433

出　　处：《中国肿瘤生物治疗杂志》2017年第2期103-111,共9页Chinese Journal of Cancer Biotherapy

基　　金：国家重点基础研究发展规划资助项目(No.2015CB554000);国家自然科学基金重大研究计划集成资助项目(No.91529305)~~

摘　　要：慢性炎症恶性转化是绝大多数癌症发生发展的共有过程。根据基因组学、体细胞变异/表观遗传影响的信号通路和流行病学等研究形成的证据链,笔者提出了癌症进化发育(cancer evolution-development,Cancer Evo-Dev)的新理论框架:先天免疫遗传与后天环境暴露的交互作用引发并维持了慢性非可控性炎症;炎症分子持续反式激活胞苷脱氨酶,该类酶被激活后发挥炎-癌转化桥梁的作用,诱导产生大量体细胞突变;绝大多数变异细胞被生存竞争淘汰,少数则通过体细胞变异和炎症相关表观遗传修饰改变了信号转导模式,经去分化过程而获得干性特性,通过并适应了炎症微环境的选择,发展成癌症起始细胞;这一过程遵循"变异-选择-适应"的进化规律。癌症进化发育学的提出不仅有利于阐明炎-癌转化的一般规律,而且对癌症的特异性预防、预测和靶向治疗有重要指导作用。Malignant transformation induced by chronic inflammation represents a common process of carcinogenesis for the majority of cancers. Authors presented a novel theory framework of cancer evolution-development （Cancer Evo-Dev） based on the evidence chains from genome researches, somatic mutations/epigenetic alterations-related signaling-pathway studies, and epidemiological investigations. The central contents of this theory include the following aspects： the interactions of genetic predispositions of key immune/inflammatory molecules and environmental exposures induce and maintain the chronic non-resolving inflammation. Under the microenvironment of non-resolving inflammation, cytidine deaminases are persistently trans-activated by proinflammatory factors and bridge chronic inflammation and cancers by promoting the generation of vast somatic mutations. Most mutant cells are eliminated in the hostile inflammatory microenvironments, only a small percentage of the mutant cells undergo de-differentiation to acquire the characteristics of “stem-ness” via altering signaling-pathways by somatic mutations and inflammation-related epigenetic modifications, and develop into cancer initiating cells. This carcinogenic process follows the evolution regulation of “mutation-selection-adaptation”. Cancer Evo-Dev not only facilitates understanding the basic mechanism of inflammation-cancer transformation, but also contributes to the development of specific prophylaxis, prediction, and targeted therapy of cancers.

关 键 词：癌症 炎症 进化 发育 肝细胞癌 结直肠癌 乙肝病毒 

分 类 号：R730.2[医药卫生—肿瘤]