Liver Unit, Department of Internal Medicine, Hospital Universitari Vall d'Hebrón, Barcelona, Spain.
Dis Markers. 2011;31(3):181-90. doi: 10.3233/DMA-2011-0841.
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, representing also the main cause of death among cirrhotic patients. In contrast to most other solid tumors, the underlying cirrhotic liver disease in HCC patients greatly impairs tumor related prognosis, conferring this neoplasm a unique situation, in which accurate prognostic prediction is a relevant and unmet need. Although clinical staging systems have improved significantly and now comprise tumor characteristics, liver function and patient performance status, the integration of molecular data into these algorithms is still hypothetical. Molecular profiling of HCC has led to a better understanding of the physiopathology of this neoplasm and has allowed developing novel therapeutic approaches (e.g. molecular targeted therapies) for a tumor previously considered as therapy-refractory. Integrative analysis of different reported genomic datasets has revealed common subclasses between different studies, highlighting their biological relevance in HCC. Gene signatures derived from tumors and from the adjacent tissue have been able to differentiate subclasses with different outcomes and have been proposed as potential predictive markers in the clinical setting. Genomic characterization of surrounding non-tumor tissue might be of particular interest to identify patients at high risk of developing HCC and therefore to select those patients that would benefit of potential chemopreventive strategies. Epigenetic analyses (methylation and miRNA profiling) are adding up to the knowlegde derived from gene expression data and should not be forgotten in the molecular diagnosis of HCC. Integrative analyses of genetic and epigenetic information of the tumor and the surrounding tissue should be used to identify novel biomarkers and therapeutic targets in HCC, to improve existing treatment algorithms and to eventually design a more personalized medicine in this devastating disease.
肝细胞癌 (HCC) 是全球最致命的癌症之一，也是肝硬化患者死亡的主要原因。与大多数其他实体瘤不同，HCC 患者的基础肝硬化疾病极大地影响了与肿瘤相关的预后，使这种肿瘤处于一种独特的境地，即准确的预后预测是一种相关且未满足的需求。尽管临床分期系统有了显著改善，现在包括肿瘤特征、肝功能和患者身体状况，但将分子数据纳入这些算法仍然是假设的。HCC 的分子谱分析使人们对这种肿瘤的病理生理学有了更好的理解，并为以前被认为是治疗抵抗的肿瘤开发了新的治疗方法（例如分子靶向治疗）。对不同报道的基因组数据集的综合分析揭示了不同研究之间的常见亚类，突出了它们在 HCC 中的生物学相关性。源自肿瘤和相邻组织的基因特征能够区分具有不同结局的亚类，并被提议作为临床环境中的潜在预测标志物。对周围非肿瘤组织的基因组特征进行分析可能特别有趣，可以识别出发生 HCC 风险较高的患者，从而选择那些可能受益于潜在化学预防策略的患者。表观遗传分析（甲基化和 miRNA 谱分析）增加了来自基因表达数据的知识，在 HCC 的分子诊断中不应被忽视。应综合分析肿瘤和周围组织的遗传和表观遗传信息，以确定 HCC 中的新型生物标志物和治疗靶点，改进现有的治疗算法，并最终在这种毁灭性疾病中设计更个性化的治疗方法。
