Nakata Takenari, Seki Naohiko, Miwa Shire, Kobayashi Akira, Soeda Junpei, Nimura Yoshinori, Kawasaki Seiji, Miyagawa Shinichi
Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, 390-8621, Japan.
Hepatogastroenterology. 2008 May-Jun;55(84):865-72.
BACKGROUND/AIMS: The prognosis of hepatocellular carcinoma (HCC) is poor because of frequent intrahepatic metastasis (IM) or multicentric carcinogenesis (MC). This study compared the effectiveness of microarray analysis in the diagnosis of these 2 forms with that of conventional histopathological diagnosis. The aim was to identify IM- or MC-associated genes through delineation of the clonality of multinodular liver cancer.
The clonal relationship of 23 tumor foci obtained from 11 surgically resected liver specimens was investigated by genome-wide expression profiling via an in-house cDNA microarray consisting of 4,608 genes.
The gene expression signature of primary HCCs with IM was very similar to that of their corresponding IMs, implying that genes favoring progression of metastasis were initiated in the primary tumors. In comparison, different gene expression was observed in multicentric HCCs. The gene for adrenomedullin, which has been identified as a lead gene in the gene expression signature, was overexpressed in HCCs with IM, as confirmed by real time-PCR and immunohistochemistry.
Analysis of expression profiles by microarray could provide a reliable method of delineating the clonal relationship of multiple nodules of liver cancer and identifying metastasis-associated genes. Adrenomedullin is a factor associated with progression of IM in human HCC.
背景/目的：由于肝细胞癌（HCC）频繁发生肝内转移（IM）或多中心癌变（MC），其预后较差。本研究比较了基因芯片分析在这两种形式诊断中的有效性与传统组织病理学诊断的有效性。目的是通过描绘多结节肝癌的克隆性来鉴定与IM或MC相关的基因。
通过由4608个基因组成的自制cDNA芯片，对从11例手术切除的肝脏标本中获得的23个肿瘤灶的克隆关系进行全基因组表达谱分析。
伴有IM的原发性肝癌的基因表达特征与其相应的IM非常相似，这意味着促进转移进展的基因在原发性肿瘤中就已启动。相比之下，多中心肝癌中观察到不同的基因表达。通过实时PCR和免疫组织化学证实，在伴有IM的肝癌中，已被确定为基因表达特征中的主导基因的肾上腺髓质素基因过度表达。
通过基因芯片分析表达谱可以提供一种可靠的方法来描绘肝癌多个结节的克隆关系并鉴定与转移相关的基因。肾上腺髓质素是人类肝癌中与IM进展相关的一个因素。
