“癌症进化发育学”理论框架及其在乙肝致癌预防中的作用

发布时间：2018-02-23 17:14

本文关键词： 乙型肝炎病毒肝细胞癌癌症进化发育学预防　出处：《中国科学基金》2015年05期 　论文类型：期刊论文

【摘要】：乙肝病毒(HBV)致肝细胞癌(HCC)过程中,免疫/炎症分子遗传易感性与HBV交互作用维持了乙肝慢性化。HBV蛋白如大S抗原和HBx通过抑制免疫维持了非可控性炎症。促炎细胞因子反式激活核酸编辑酶如胞苷脱氨酶的表达,促进病毒和宿主基因组变异。绝大部分变异细胞在生存竞争中被淘汰,只有极其少数细胞通过改变细胞生存依赖的信号通路,具备了上皮细胞向间质细胞转化等逆向分化的潜能,获得了克服衰老、掠夺营养、无限增值和化疗抵抗等"干性"特征而被选择出来,成为癌症起始细胞。这类细胞逐渐适应了促癌炎症微环境,演绎了"变异—选择—适应"的进化过程。癌症进化发育学理论可能为癌症监测、预防和预后预测提供可靠生物标志和靶向治疗有效靶标。
[Abstract]:In the process of hepatitis B virus hepatitis B virus (HBV) induced hepatocellular carcinoma (HCC), The interaction between immune / inflammatory molecular genetic susceptibility and HBV maintained the expression of hepatitis B chronic. HBV proteins such as large S antigen and HBx maintained non-controllable inflammation through immunosuppressive immunostimulation. The pro-inflammatory cytokine trans-activated nucleic acid editing enzyme such as cytidine deaminase was expressed. Promoting viral and host genome mutation. Most of the mutant cells are eliminated in the competition for survival, and only a very small number of cells change the signaling pathway that cells depend on for their survival. Having the potential of reverse differentiation, such as the transformation of epithelial cells to mesenchymal cells, they were selected to overcome the "dry" characteristics of aging, pillaging, unlimited increment and resistance to chemotherapy. Become cancer initiation cells. These cells gradually adapt to the pro-inflammatory microenvironment, deducing the evolutionary process of "mutation-selection-adaptation." the evolutionary development theory of cancer may be used to monitor cancer. Prevention and prognosis prediction provide reliable biomarkers and effective targets for targeted therapy.
【作者单位】：中国人民解放军第二军医大学流行病学教研室;
【基金】：国家自然科学基金国家杰出青年科学基金项目(81025015);国家自然科学基金重大研究计划重点项目(91129301)资助
【分类号】：R512.62;R735.7

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