Budhu Anuradha S, Zipser Brian, Forgues Marshonna, Ye Qing-Hai, Sun Zongtang, Wang Xin W
Liver Carcinogenesis Group, LHC, CCR, NCI, NIH, Bethesda, MD 20892, USA.
Oncology. 2005;69 Suppl 1:23-7. doi: 10.1159/000086628. Epub 2005 Sep 19.
The current metastasis paradigm suggests that the primary tumor starts off benign but over time slowly acquires changes that provide a few rare cells within the tumor the ability to metastasize. However, this concept has been challenged by several recent studies using the microarray-based approach. We have recently found that the molecular signature of primary hepatocellular carcinoma (HCC) is very similar to that of their corresponding metastases, while it differs significantly in primary HCCs with or without metastasis. Similar findings are also evident in primary cancers of the lung, breast, and prostate. Such a signature can be used to predict the prognosis of HCC patients. Moreover, there are significant differences in the gene expression profiles of liver parenchyma among HCC patients with or without intrahepatic metastases. These findings imply that many of the metastasis-promoting genes are embedded in the primary tumors and that the ability to metastasize may be an inherent quality of the tumor from the beginning. In addition, the condition of liver parenchyma may dictate the intrahepatic metastasis potential, which is consistent with the hypothesis that the degree of viral-hepatitis-mediated liver damage or possibly the genetic makeup of individuals may play an important role in metastasis.
当前的转移模式认为，原发性肿瘤起初是良性的，但随着时间的推移会逐渐发生变化，使肿瘤内少数罕见细胞获得转移能力。然而，这一概念受到了最近几项基于微阵列方法的研究的挑战。我们最近发现，原发性肝细胞癌（HCC）与其相应转移灶的分子特征非常相似，而在有无转移的原发性HCC中则有显著差异。在肺癌、乳腺癌和前列腺癌的原发性肿瘤中也有类似的发现。这样的特征可用于预测HCC患者的预后。此外，有无肝内转移的HCC患者肝实质的基因表达谱存在显著差异。这些发现表明，许多促进转移的基因存在于原发性肿瘤中，转移能力可能从一开始就是肿瘤的固有特性。此外，肝实质状况可能决定肝内转移潜能，这与病毒性肝炎介导的肝损伤程度或个体基因组成可能在转移中起重要作用的假设是一致的。
