Patterns of expression of cytochrome P450 genes in progression of hepatitis C virus-associated hepatocellular carcinoma.
Patterns of expression of cytochrome P450 genes in progression of hepatitis C virus-associated hepatocellular carcinoma.
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DOI：
10.3892/ijo.27.3.661
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发表时间：
2005-09
影响因子：
5.2
通讯作者：
Ryouichi Tsunedomi;N. Iizuka;Y. Hamamoto;S. Uchimura;Takanobu Miyamoto;T. Tamesa;Toshimasa Okada;N. Takemoto;M. Takashima;Kazuhiko Sakamoto;K. Hamada;H. Yamada‐Okabe;M. Oka
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文献类型：
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作者：
Ryouichi Tsunedomi;N. Iizuka;Y. Hamamoto;S. Uchimura;Takanobu Miyamoto;T. Tamesa;Toshimasa Okada;N. Takemoto;M. Takashima;Kazuhiko Sakamoto;K. Hamada;H. Yamada‐Okabe;M. Oka
细胞色素 P450 (CYP) 基因参与肝细胞癌 (HCC) 的发病机制。为了检查丙型肝炎病毒 (HCV) 感染肝脏引起的 HCC 中 CYP 表达的变化，我们使用了来自 50 个 HCV 相关 HCC、5 个 HCV 感染非肿瘤肝脏和 6 个 HCV 阴性正常肝脏样本的 27 个 CYP 的寡核苷酸阵列数据。原发性 HCC 进展的特点是肿瘤分化程度降低、静脉侵犯频率增加和肿瘤大小增大。根据肿瘤分化，自组织图谱 (SOM) 将 27 个 CYP 分为四组。第一组包含 11 个 CYP，包括 CYP2C 和 CYP4F 家族，随着 HCV 感染的肝脏进展为分化程度较低的 HCC，它们的表达量降低。第二组包含 CYP-IID、CYP3A7 和 CYP27A1，这些基因表现出高分化 HCC 特异性的高水平表达。第三组含有 5 种甾醇代谢 CYP，其水平在 HCV 感染的肝脏中低于 HCV 未感染的肝脏。最后一组包括 CYP2E1 和 CYP3A 家族。在27种CYP中，有静脉侵犯的HCC中7种（CYP2B6、CYP-IIC、CYP2C9、CYP2C19、CYP3A5、CYP4F3和CYP27A1）的水平显着降低，2种（CYP2E1和CYP4F2）的水平在有静脉侵犯的HCC中略低于无静脉侵犯的HCC。 CYP-IIC 和 CYP2C9 的水平与肿瘤大小呈负相关。相反，CYP51A1 的水平与肿瘤大小呈正相关。我们目前的研究表明，特定 CYP 的表达随着 HCV 相关 HCC 的进展而改变。这些 CYP 可以作为 HCV 相关 HCC 进展的标志物和治疗的分子靶点。
Cytochrome P450 (CYP) genes are involved in the pathogenesis of hepatocellular carcinoma (HCC). To examine changes in expression of CYPs in HCC arising from hepatitis C virus (HCV)-infected liver, we used oligonucleotide array data of 27 CYPs from samples of 50 HCV-associated HCCs, five HCV-infected non-tumorous livers, and six HCV-negative normal livers. Progression of primary HCC can be characterized by decrease in the grade of tumor differentiation, increased frequency of venous invasion and increased tumor size. On the basis of tumor differentiation, the self-organizing map (SOM) classified the 27 CYPs into four groups. The first group contained 11 CYPs, including the CYP2C and CYP4F families, that showed decreased expression in parallel with progression of HCV-infected liver to HCC with less differentiation. The second group contained CYP-IID, CYP3A7 and CYP27A1, genes that showed high levels of expression specific to well differentiated HCC. The third group contained 5 sterol-metabolizing CYPs with levels lower in HCV-infected livers than in HCV-uninfected livers. The last group included the CYP2E1 and CYP3A families. Among the 27 CYPs, levels of 7 (CYP2B6, CYP-IIC, CYP2C9, CYP2C19, CYP3A5, CYP4F3 and CYP27A1) were significantly lower and levels of 2 (CYP2E1 and CYP4F2) were slightly lower in HCC with venous invasion than in HCC without venous invasion. Levels of CYP-IIC and CYP2C9 were inversely associated with tumor size. In contrast, levels of CYP51A1 were positively associated with tumor size. Our present study revealed that expression of specific CYPs was altered in conjunction with progression of HCV-associated HCC. These CYPs may serve as markers of progression and molecular targets for treatment of HCV-associated HCC.