Mas Valeria R, Maluf Daniel G, Archer Kellie J, Yanek Kenneth, Kong Xiangrong, Kulik Laura, Freise Chris E, Olthoff Kim M, Ghobrial Rafik M, McIver Paula, Fisher Robert
Division of Transplantation, Department of Surgery, Virginia Commonwealth University, Richmond, Virginia, USA.
Mol Med. 2009 Mar-Apr;15(3-4):85-94. doi: 10.2119/molmed.2008.00110. Epub 2008 Dec 15.
The role of chronic hepatitis C virus (HCV) in the pathogenesis of HCV-associated hepatocellular carcinoma (HCC) remains controversial. To understand the transition from benign to malignant, we studied the gene expression patterns in liver tissues at different stages, including normal, cirrhosis, and different HCC stages. We studied 108 liver tissue samples obtained from 88 distinct patients (41 HCV-cirrhotic tissues, 17 HCV-cirrhotic tissues from patients with HCC, and 47 HCV-HCC tissues). Differentially expressed genes (DEG) were studied by use of high-density oligonucleotide arrays. Among probe sets identified as differentially expressed via the F test, all pairwise comparisons were performed. Cirrhotic tissues with and without concomitant HCC were further evaluated, and a classifier was used to predict whether the tissue type was associated with HCC. Differential expression profiles were analyzed using Interaction Networks and Functional Analysis. Characteristic gene signatures were identified when normal tissue was compared with cirrhosis, cirrhosis with early HCC, and normal with HCC. Pathway analysis classified the cellular and biological functions of the DEG as related to cellular growth and proliferation, cell death and inflammatory disease in cirrhosis; cell death, cell cycle, DNA replication, and immune response in early HCCs; and cell death, cell growth and proliferation, cell cycle, and DNA repair in advanced HCCs. Characteristic gene signatures were identified at different stages of HCV-HCC progression. A set of genes were identified to predict whether the cirrhotic tissue was associated with HCC.
慢性丙型肝炎病毒（HCV）在HCV相关肝细胞癌（HCC）发病机制中的作用仍存在争议。为了解从良性到恶性的转变过程，我们研究了不同阶段肝脏组织中的基因表达模式，包括正常、肝硬化以及不同的HCC阶段。我们研究了从88名不同患者获取的108份肝脏组织样本（41份HCV肝硬化组织、17份来自HCC患者的HCV肝硬化组织以及47份HCV-HCC组织）。通过使用高密度寡核苷酸阵列研究差异表达基因（DEG）。在通过F检验确定为差异表达的探针集中，进行了所有成对比较。对伴有和不伴有HCC同时存在的肝硬化组织进行了进一步评估，并使用一种分类器来预测组织类型是否与HCC相关。使用相互作用网络和功能分析对差异表达谱进行分析。当将正常组织与肝硬化、肝硬化与早期HCC以及正常与HCC进行比较时，鉴定出了特征性基因特征。通路分析将DEG的细胞和生物学功能分类为与肝硬化中的细胞生长和增殖、细胞死亡及炎症性疾病相关；与早期HCC中的细胞死亡、细胞周期、DNA复制及免疫反应相关；以及与晚期HCC中的细胞死亡、细胞生长和增殖、细胞周期及DNA修复相关。在HCV-HCC进展的不同阶段鉴定出了特征性基因特征。鉴定出了一组基因来预测肝硬化组织是否与HCC相关。
