Molecular Diagnosis of Multistage Hepatocarcinogenesis
Molecular Diagnosis of Multistage Hepatocarcinogenesis
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DOI：
10.1093/jjco/hyq099
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发表时间：
2010-09-01
影响因子：
2.4
通讯作者：
Masugi, Yohei
中科院分区：
文献类型：
--
作者：
Sakamoto, Michiie;Effendi, Kathryn;Masugi, Yohei
人类肝细胞癌被认为是多阶段癌发生的良好模型，因为从慢性肝病到晚期人类肝细胞癌的恶性步骤相对清晰。我们讨论了肝癌发生过程中不同分子通路的激活，这在病理多阶段人肝细胞癌的诊断中特别有用。在慢性肝病中，基因表达特征以及肝纤维化程度可以帮助我们预测人肝细胞癌的发展或人肝细胞癌治疗后的生存结局。一些基因，如HSP 70，CAP 2和GPC 3，已被确定为早期人类肝细胞癌的潜在生物标志物。经典的癌基因或肿瘤抑制基因，如β-连环蛋白和p53，在从早期到晚期人类肝细胞癌的进展过程中发生突变。此外，肝细胞特征如CK 19在晚期人肝细胞癌中的存在可用作侵袭性人肝细胞癌的预测因子。虽然在多阶段肝癌发生的诊断方面取得了许多进展，但我们仍然需要更多有用的标志物来更准确地评估肝癌发生的每个步骤，以更好地选择治疗方案，这将促进未来的分子靶向治疗。
Human hepatocellular carcinoma is recognized as a good model for multistage carcinogenesis, as the malignant steps from chronic liver disease through to advanced human hepatocellular carcinoma are relatively clear. We address the activation of different molecular pathways during hepatocarcinogenesis that is especially useful in the diagnosis of pathological multistage human hepatocellular carcinoma. In chronic liver disease, the gene-expression signature as well as the degree of liver fibrosis could help us to predict the development of human hepatocellular carcinoma or survival outcome after treatment for human hepatocellular carcinoma. Several genes, such as HSP70, CAP2 and GPC3, have been identified as potential biomarkers for early human hepatocellular carcinoma. Classical oncogenes or tumor suppressor genes, such as beta-catenin and p53, are mutated during the progression from early to advanced human hepatocellular carcinoma. Also, the presence of hepatoblastic feature like CK19 in advanced human hepatocellular carcinoma can be used as a predictor of aggressive human hepatocellular carcinoma. Although many advances have been made in the diagnosis of multistage hepatocarcinogenesis, we still need further useful markers to more precisely evaluate each step of hepatocarcinogenesis for better treatment choices, and that will promote future molecular-targeted therapy.