Iizuka Norio, Oka Masaaki, Yamada-Okabe Hisafumi, Hamada Kenji, Nakayama Hironobu, Mori Naohide, Tamesa Takao, Okada Toshimasa, Takemoto Norikazu, Matoba Katsuhiro, Takashima Motonari, Sakamoto Katsuhiko, Tangoku Akira, Miyamoto Takanobu, Uchimura Shunji, Hamamoto Yoshihiko
Department of Bioregulatory Function, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Int J Oncol. 2004 Mar;24(3):565-74.
Chronic infection with hepatitis B or C virus (HBV or HCV) is the most clearly established risk factor for hepato-cellular carcinoma (HCC). One type of HCC (non-B, non-C HCC) also appears to develop in patients negative for both HBV and HCV. Using a supervised learning method, we investigated gene expression in 11 non-B, non-C HCCs with high-density oligonucleotide microarrays, and compared the patterns of gene expression with those of HBV-infected HCCs (B-type HCCs) and HCV-infected HCCs (C-type HCCs) in the previous dataset. Our gene selection identified 112 and 64 genes that were differentially expressed in non-B, non-C HCC in comparison with B- and C-type HCCs, respectively. In both gene selections, we found that the false discovery rate, the percentage of genes identified by chance, was less than 5%. Additionally, in combination with the previous data, our present data revealed a set of genes specific to each type of B- and C-type HCCs and non-B, non-C HCC. Among these, an interferon-induced gene, IFI27, was differentially expressed among all three types of HCCs, and this result was confirmed by RT-PCR. Thus, our present study provides a framework to characterize the molecular features in the three subtypes of HCC with different viral origin.
慢性乙型或丙型肝炎病毒(HBV或HCV)感染是肝细胞癌(HCC)最明确的既定危险因素。一种类型的HCC(非B、非C型HCC)似乎也会在HBV和HCV均呈阴性的患者中发生。我们采用监督学习方法,利用高密度寡核苷酸微阵列研究了11例非B、非C型HCC的基因表达,并将基因表达模式与先前数据集中HBV感染的HCC(B型HCC)和HCV感染的HCC(C型HCC)进行了比较。我们的基因筛选分别鉴定出112个和64个在非B、非C型HCC中与B型和C型HCC相比差异表达的基因。在这两次基因筛选中,我们发现错误发现率(即偶然鉴定出的基因百分比)均低于5%。此外,结合先前的数据,我们目前的数据揭示了一组分别特定于B型和C型HCC以及非B、非C型HCC的基因。其中,一种干扰素诱导基因IFI27在所有三种类型的HCC中均有差异表达,这一结果通过逆转录聚合酶链反应(RT-PCR)得到了证实。因此,我们目前的研究提供了一个框架,用于表征具有不同病毒起源的HCC三种亚型的分子特征。