The identification of molecular mechanisms in human hepatocellular carcinoma

Distinct expression patterns between hepatitis B virus- and hepatitis C virus-infected hepatocellular carcinoma

李俊鋒(Chun-Feng Lee)

指導教授 ： 李寬容

國立清華大學/生命科學院/分子醫學研究所/博士(2009年)

摘要

Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide. Major risk factors for HCC are chronic hepatitis resulting from infection with HBV or HCV and exposure to various exogenous carcinogens. To identify any useful biomarkers indicating virus-specific hepatocarcinogenic process, differential mRNA expression in 32 patients with HBV- / HCV-associated HCC was investigated by means of cDNA microarrays consisting of 886 genes. Among them, the up-regulation of 7 genes were involved in HBV-associated HCC, such as RPS5 (protein synthesis), KRT8 (cytoskeletal organization), CFLAR (apoptosis related genes), ATP5F1 (transport), IGFBP2 (cell membrane receptor related genes), MAP3K5 (signal transduction or transcription related genes), and MMP9 (metastasis-related genes). The up-regulated genes in HCV-infected group included 4 genes, such as VIM (cell structure), ACTB (cell structure), GAPD (glycolysis) and CD58 (cell adhesion). The different genes between HBV- and HCV-associated HCC indicate that the pathogenetic mechanisms of hepatocarcinogenesis may be different according to the viral factor, HBV and HCV. These results suggest that HBV and HCV cause hepatocarcinogenesis by different mechanisms and provide novel tools for diagnosis and treatment of HBV- and HCV- associated HCC.The high mortality associated with this disease is mainly attributed to its high tendency of metastasis. In fact, local lymph node and blood metastasis could occur at early stage, which may be the key factors of its recurrence and poor prognosis. Therefore, a better understanding for the molecular mechanism of metastasis can improve prevention and treatment of HCC. Our results of the cDNA microarray demonstrated that 25 up-regulated genes that included cell adhesion related genes (CD58, ITGAM, ITGB5, OPCML), cell membrane receptor (CD86, JUN, MET, EPHA2, EGFR), cell death regulator (BNIP3, SEMA4D), intracellular signaling related genes (ARHGDIG, RAC3, IGFBP3, F2R), growth/differentiation factor (VEGFC), cell cycle regulator (CCND1, CDK4), and other genes (TIMP3, UBE2A, YES1, POR, MMP13, MMP2). The 48 down-regulated genes included cell adhesion related genes (DSP, PCDHGC3, ITGB4, ITGA3, CTNNA1, CDH1), cell cycle regulator (CDC25B, CDK5, CCND2, MAPRE1, PPM1D, ATR, PPP2R5A), intracellular signaling related genes (MAPK14, MAPK7, MAPK4, SCYB13, STAT5B, SERPINB1, SERPINB2, SH3BP2, GPRK6, RAGB, PTPRF), cell membrane receptor (EPHB6, KAI1, SCYA25, MGLL, IFNAR1, IGFBP6), metabolic enzyme (SPINT2, PPP2R5A, PTPN2, DNASE1L3, CTSL), cell death regulator (CASP3, PDCD10), DNA damage response related genes (ATR, XRCC5, MDM2), growth/differentiation factor (BMP5, KRT4, KRT13, CTGF), and other genes (HSPA4, RXRA, UBE1L, SLC25A5).
The result of this study may help clinicians to predict metastasis of lymph nodes and assist researchers in identifying novel therapeutic targets for metastatic HCC patients. However, it is more important to further analyze each gene in detail to elucidate the mechanism of lymph node metastasis in HCC.

關鍵字

人類肝細胞癌 ； 生物晶片 ； 雷射擷取顯微切開 ； 維陣列晶片 ； 淋巴轉移 ； 基因表現

並列摘要

無資料

並列關鍵字

hepatocellular carcinoma ； biochip ； laser capture microdissection ； microarray ； lymphatic metastasis ； gene expression

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