Research progress and clinical implication on origin cells of intrahepatic cholangiocarcinoma
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摘要: 肝内胆管癌(intrahepatic cholangiocarcinoma,iCCA)是一种预后较差的上皮性恶性肿瘤,发病率和死亡率逐年上升。以化疗为主的标准治疗方案效果不佳,亟需开发有效的精准治疗新策略。iCCA在组织形态以及分子表达水平上表现出的高度异质性,对临床精准治疗造成了巨大阻碍。肿瘤异质性的产生是多种复杂因素相互作用的结果,包括致病因素、不同的基因突变、分子表达谱的可塑性变化以及不同的潜在起源细胞等。目前在小鼠模型中使用遗传谱系示踪系统明确了胆管上皮细胞、肝细胞或肝母细胞都可能是iCCA的起源细胞。本文系统性回顾了这些肿瘤起源细胞的相关研究,并认为将iCCA肿瘤起源细胞的相关信息综合到当前的组织病理学和分子分型系统中,有望对iCCA的临床精准诊疗提供指导和借鉴。Abstract: Intrahepatic cholangiocarcinoma (iCCA) is an epithelial malignancy with a poor prognosis and an ever-increasing morbidity and mortality rates in recent years. Chemotherapy-based standard treatment is ineffective, and novel effective precision treatment strategies are urgently needed. However, iCCA is characterized by high heterogeneity in tissue morphology and molecular profiles, which is a considerable obstacle to clinical precision therapy. Tumor heterogeneity develops due to the interaction of multiple complex factors, including pathogenic factors, different genetic mutations, plasticity in molecular profiles, and different potential origin cells. Current genetic lineage tracing systems in mouse models have identified bile duct cells, hepatocytes, and hepatoblasts as possible origin cells of iCCA. This systematic review of the relevant studies on these tumor origin cells suggests that integrating the relevant information about iCCA on origin cells into current histopathological and molecular classification system should help guide the precise diagnosis and treatment of iCCA.
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Key words:
- intrahepatic cholangiocarcinoma (iCCA) /
- heterogeneity /
- origin cells
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