Molecular Pathogenesis of Hepatocellular Carcinoma

Full Article


Hong Kong J Radiol 2012;15(Suppl):S23-8

Liver cancer, which consists predominantly of hepatocellular carcinoma, is one of the most frequently occurring cancers and the third most common cause of cancer death worldwide. Hepatocarcinogenesis follows a multistep process evolving from cirrhosis / chronic hepatitis to dysplastic nodules and ultimately malignant tumours. Recent advances in molecular methods have led to a growing understanding of the underlying mechanisms of hepatocarcinogenesis. Hepatocarcinogenesis is closely associated with allelic losses, chromosomal changes, gene mutations, and epigenetic alterations. Some of these alterations show a stepwise increase at different stages of hepatocarcinogenesis. Chromosomal, genetic, and epigenetic abnormalities can lead to deregulation in many cell signalling pathways implicated in tumour proliferation, progression, and survival. Discoveries and insight into these complex pathways have created opportunities for targeted agents and new therapeutic approaches for this disease. More recent evidence also suggests the involvement of aberrant microRNA expression and the concept of liver-specific cancer stem cells in hepatocarcinogenesis. Detailed understanding of the molecular pathogenesis is crucial for the development of new therapeutic approaches against hepatocellular carcinoma. This article summarises the molecular mechanisms currently implicated in the pathogenesis of hepatocellular carcinoma and their potential roles in improving the clinical management of this disease.





肝癌主要包括肝細胞癌,是最常見的癌症之一,亦在全球致命癌症中排行第三。肝癌的發病是從肝 硬化或慢性肝炎演變成非典型增生的結節而最終造成惡性腫瘤的一個牽涉多個步驟的過程。分子生 物學的最新發展使人們對肝癌發病的潛在機制有更多認識。肝癌與等位基因損失、染色體變化、基 因突變和表觀遺傳改變密切相關,而這些改變在肝癌的不同階段續漸遞增。染色體、遺傳和表觀遺 傳異常可導致許多牽連細胞通訊路線出現不規則、腫瘤增殖、惡化及生存。發現和洞悉這些複雜的 分子病變機制造就了標靶藥物和新療法的誕生。最新的實證亦顯示了microRNA的異常表達和肝臟特 有的癌幹細胞有參與肝癌發病機制。詳細認識分子發病機制對肝癌的新治療方案的發展至為重要。 本文總結了肝癌病發所牽涉的分子機制,以及它們在改善肝癌臨床管理中的角色。