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疾病。它是导致癌症死亡的第四大原因，每年约有100万人死于癌症。肝细胞癌（HCC）是原发性肝癌的主要类型。HCC被认为是一种绝症，目前在发现有效的治疗方法方面进展甚微。这主要是由于缺乏早期诊断的方法和缺乏与HCC发展相关的表型变化的信息。我们的目标是确定负责HCC发生的常见基因簇，发现对病毒性肝炎介导的HCC至关重要的新基因以及转移所必需的基因。例如，通过比较具有不同程度发展为肝细胞癌风险的慢性肝病患者的肝脏样本，我们已经确定了独特的指纹，可能有助于诊断早期发病的肝癌患者。通过比较伴有或不伴有转移的肝细胞癌，我们已经确定了一种分子特征，可用于预测有可能发生转移或复发的肝癌患者。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。我们还确定了几个潜在的治疗靶点，可用于消除肝癌细胞或阻止转移进展。目前，我们正在探索这些基因在肝癌发生和转移中的作用。我们的发现非常富有成效，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肿瘤进化的范式。显然，基因表达谱扩展了我们对肝癌发生的全局变化的认识，并为这种疾病的分子机制提供了许多见解。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志物，以及直接临床干预该疾病的潜在治疗靶点。

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.