Involvement of c-myc-regulated genes in hepatocellular carcinoma related to genotype-C hepatitis B virus
Involvement of c-myc-regulated genes in hepatocellular carcinoma related to genotype-C hepatitis B virus
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DOI：
10.1007/s00432-006-0094-8
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发表时间：
2006-07-01
影响因子：
3.6
通讯作者：
Oka, Masaaki
中科院分区：
文献类型：
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作者：
Iizuka, Norio;Tsunedomi, Ryouichi;Oka, Masaaki
目的：本研究的目的是阐明基因型C型B型肝炎病毒（HBV）引起肝细胞癌（HCC）的分子基础。研究方法：我们使用DNA微阵列技术比较了15例HCC和5例非肿瘤性肝脏的分子谱，所有这些都与基因型C HBV感染相关。结果：我们的监督学习确定了237个基因，其表达在HCC和非肿瘤肝脏之间存在差异。该结果通过0%的错误发现率进行验证。35个和202个基因的表达水平在HCC中分别高于和低于非肿瘤性肝脏。在237个基因中，我们突出了肿瘤中前35个上调和前35个下调的基因。有趣的是，当排除重叠基因时，12个（例如，NM 23-H2、MCM 7、PARP 1、YWHAH、HSPB 1和MSH 2）和前34个上调基因中的5个（例如，在前33位下调基因中，MT 1A和MT3均为c-myc调控基因。5个随机选择的基因（MCM 7，UBE 2L 3，PPIA，CXCL 12和ASS）的微阵列数据通过定量实时逆转录聚合酶链反应进行了确认。结论：我们的研究结果表明，许多c-myc调控的基因参与基因型C HBV相关的肝癌，表明c-myc是与基因型C HBV的肝癌活动。
Purpose: The purpose of this study was to elucidate the molecular basis of hepatocellular carcinoma (HCC) caused by genotype-C hepatitis B virus (HBV). Methods: We compared molecular profiles of 15 HCCs and five non-tumorous livers, all of which were associated with genotype-C HBV infection, using DNA microarray technology. Results: Our supervised learning identified 237 genes whose expression differed between HCCs and non-tumorous livers. This result was validated by a false discovery rate of 0%. Levels of expression of 35 and 202 genes were higher and lower, respectively, in HCCs than in non-tumorous livers. Among the 237 genes, we highlighted the top 35 upregulated and top 35 downregulated genes in tumor. Interestingly, when overlapping genes were excluded, 12 (e.g., NM23-H2, MCM7, PARP1, YWHAH, HSPB1, and MSH2) of the top 34 upregulated genes and five (e.g., MT1A and MT3) of the top 33 downregulated genes were c-myc-regulated genes. The microarray data for five randomly selected genes (MCM7, UBE2L3, PPIA, CXCL12, and ASS) were confirmed by quantitative real-time reverse transcription-polymerase chain reaction. Conclusions: Our results indicate that many c-myc-regulated genes are involved in genotype-C-HBV-related HCC, suggesting that c-myc is related to the hepatocarcinogenic activity of genotype-C HBV.