Molecular profiling of human hepatocellular cancer

人类肝癌在美国的发病率越来越高，是世界上第五大最常见的恶性肿瘤。它是癌症死亡的第四大原因，估计每年有100万人死于癌症。肝细胞癌是原发性肝癌的一种主要类型。肝细胞癌被认为是一种晚期疾病，目前，在发现导致消退的有效治疗方法方面进展甚微。这在很大程度上是由于缺乏早期诊断的方法，以及缺乏与肝细胞癌发展相关的表型变化的信息。我们的目标是确定共同的基因簇，负责肝癌的发生，并发现新的对病毒性肝炎介导的肝癌至关重要的基因以及转移所必需的基因。例如，通过比较患有不同程度肝细胞癌的慢性肝病患者的肝脏样本，我们已经确定了独特的指纹，这些指纹可能有助于诊断早期肝癌患者。通过比较有无转移的肝细胞癌，我们已经确定了一个分子标记，可以用来预测肝癌患者发生转移或复发的可能性。此外，我们正在通过特别关注免疫细胞的功能和肝癌进展中的炎症过程来研究肝脏微环境在转移和复发中的作用。我们还确定了几个可能用于消除肝癌细胞或阻止转移进展的潜在治疗靶点。目前，我们正在探索这些基因在肝癌发生和转移中的作用。我们的发现是非常有成效的，因为它们不仅可以为患者管理提供实用工具，而且还可以挑战当前的肿瘤进化范式。显然，基因表达谱扩大了我们对肝癌发生的全球变化的了解，并为这种疾病的分子机制提供了大量的见解。此外，这些研究无疑将有助于建立具有潜在诊断和预后价值的新标记物，以及直接临床干预的潜在治疗靶点。

Human liver cancer, with increasing occurrence in the United States, is the 5th most prevalent malignant disease in the world. It is the fourth leading cause of cancer mortality, which accounts for an estimated 1 million deaths annually. Hepatocellular carcinoma (HCC) is a major type of primary liver cancer. HCC is considered to be a terminally ill disease and currently, there is little progress toward the discovery of efficient therapies leading to regression. This is due largely to the lack of a method for early diagnosis and the lack of information on the phenotypic changes associated with the development of HCC. Our goals are to identify common gene clusters that are responsible for the genesis of HCC and to discover new genes critical for viral hepatitis-mediated HCC as well as genes necessary for metastasis. For example, by comparing liver samples from chronic liver disease patients with varying degrees of risk for developing hepatocellular carcinoma, we have identified unique fingerprints that may be useful in diagnosing patients with early onset of liver cancer. By comparing hepatocellular carcinoma with or without accompanying metastasis, we have identified a molecular signature that can be used to predict liver cancer patients with a potential to develop metastasis or recurrence. In addition, we are examining the role of the liver microenvironment in metastasis and recurrence by focusing particularly on the functions of immune cells and the inflammatory process in liver cancer progression. We have also identified several potential therapeutic targets that may be used to eliminate liver cancer cells or stop metastatic progression. Currently, we are exploring the roles of these genes in liver cancer initiation and metastasis. Our findings have been extremely fruitful as they may not only offer utilities to patient managements, but also challenge the current paradigm of tumor evolution. Clearly, gene expression profiling has expanded our knowledge of the global changes that occur in liver cancer, and has provided numerous insights into the molecular mechanisms of this disease. In addition, these studies will undoubtedly contribute to the establishment of novel markers with potential diagnostic and prognostic value, as well as potential therapeutic targets for direct clinical intervention of this disease.