Castelli Germana, Pelosi Elvira, Testa Ugo
Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome 00141, Italy.
Cancers (Basel). 2017 Sep 20;9(9):127. doi: 10.3390/cancers9090127.
Liver cancer is the second most common cause of cancer-related death. The major forms of primary liver cancer are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Both these tumors develop against a background of cirrhotic liver, non-alcoholic fatty liver disease, chronic liver damage and fibrosis. HCC is a heterogeneous disease which usually develops within liver cirrhosis related to various etiologies: hepatitis B virus (HBV) infection (frequent in Asia and Africa), hepatitis C virus (HCV), chronic alcohol abuse, or metabolic syndrome (frequent in Western countries). In cirrhosis, hepatocarcinogenesis is a multi-step process where pre-cancerous dysplastic macronodules transform progressively into HCC. The patterns of genomic alterations observed in these tumors were recently identified and were instrumental for the identification of potential targeted therapies that could improve patient care. Liver cancer stem cells are a small subset of undifferentiated liver tumor cells, responsible for cancer initiation, metastasis, relapse and chemoresistance, enriched and isolated according to immunophenotypic and functional properties: cell surface proteins (CD133, CD90, CD44, EpCAM, OV-6, CD13, CD24, DLK1, α2δ1, ICAM-1 and CD47); the functional markers corresponding to side population, high aldehyde dehydrogenase (ALDH) activity and autofluorescence. The identification and definition of liver cancer stem cells requires both immunophenotypic and functional properties.
肝癌是癌症相关死亡的第二大常见原因。原发性肝癌的主要类型是肝细胞癌（HCC）和肝内胆管癌（iCCA）。这两种肿瘤均在肝硬化、非酒精性脂肪性肝病、慢性肝损伤和肝纤维化的背景下发生。HCC是一种异质性疾病，通常在与各种病因相关的肝硬化中发生：乙型肝炎病毒（HBV）感染（在亚洲和非洲常见）、丙型肝炎病毒（HCV）、慢性酒精滥用或代谢综合征（在西方国家常见）。在肝硬化中，肝癌发生是一个多步骤过程，癌前发育异常的大结节逐渐转变为HCC。最近已确定了这些肿瘤中观察到的基因组改变模式，这些模式有助于识别可能改善患者治疗的潜在靶向疗法。肝癌干细胞是未分化肝肿瘤细胞的一个小亚群，负责癌症的起始、转移、复发和化疗耐药，可根据免疫表型和功能特性进行富集和分离：细胞表面蛋白（CD133、CD90、CD44、EpCAM、OV-6、CD13、CD24、DLK1、α2δ1、ICAM-1和CD47）；与侧群、高醛脱氢酶（ALDH）活性和自发荧光相对应的功能标志物。肝癌干细胞的鉴定和定义需要免疫表型和功能特性两者兼备。
