Mount Sinai Liver Cancer Program, Mount Sinai School of Medicine, New York 10029, USA.
Semin Oncol. 2012 Aug;39(4):473-85. doi: 10.1053/j.seminoncol.2012.05.003.
Clinical management of hepatocellular carcinoma (HCC) is a complex process. Currently existing prognostic staging systems have substantially improved the clinical outcome of patients by guiding treatment decision and allocation of medical resources. However, there is still room to refine many aspects of the framework based on more precise clinical outcome prediction and understanding of HCC molecular pathogenesis. Recent development of genomic technologies has enabled survey of molecular aberrations and deregulations directly from patient specimens in a comprehensive manner. This also has provided clues to therapeutic/preventive targets that could also serve as prognostic/predictive biomarkers. Structural alterations and chemical modifications of genomic DNA have been shown to be useful to guide molecular targeted therapies in some cancers. Gene expression signatures also hold promise as a way to probe functional biological status of the tumor specimen. However, accumulated studies have revealed roadblocks toward the goal to utilize the information in clinic. In this review, we discuss the gene signature's potential application, its pros and cons as a clinical test, technical issues in assay development, and strategies for clinical deployment in the context of HCC management. Recent updates of HCC gene signatures as well as emerging alternative modalities are also overviewed.
肝细胞癌(HCC)的临床管理是一个复杂的过程。目前现有的预后分期系统通过指导治疗决策和医疗资源的分配,大大改善了患者的临床结局。然而,基于更精确的临床结局预测和对 HCC 分子发病机制的理解,仍有许多方面需要进一步完善该框架。基因组技术的最新发展使人们能够全面地直接从患者标本中检测分子异常和失调。这也为治疗/预防靶点提供了线索,这些靶点也可以作为预后/预测生物标志物。已经证明基因组 DNA 的结构改变和化学修饰可用于指导某些癌症的分子靶向治疗。基因表达谱也有望作为一种方法来探测肿瘤标本的功能生物学状态。然而,积累的研究表明,在将这些信息应用于临床方面存在障碍。在这篇综述中,我们讨论了基因特征作为临床检测的潜在应用、优缺点、检测方法开发中的技术问题以及在 HCC 管理背景下的临床应用策略。还概述了 HCC 基因特征的最新更新以及新兴的替代方式。