Molecular features of non-B, non-C hepatocellular carcinoma: a PCR-array gene expression profiling study

• Published in: Journal of hepatology Vol. 39; no. 6; pp. 1004 - 1012
• Main Authors: Kurokawa, Yukinori, Matoba, Ryo, Takemasa, Ichiro, Nakamori, Shoji, Tsujie, Masanori, Nagano, Hiroaki, Dono, Keizo, Umeshita, Koji, Sakon, Masato, Ueno, Noriko, Kita, Hiroko, Oba, Shigeyuki, Ishii, Shin, Kato, Kikuya, Monden, Morito
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01-12-2003; Elsevier
• Subjects: Aged; Aged, 80 and over; Algorithms; Biological and medical sciences; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - virology; Cryptogenic cirrhosis; DNA microarray; Expression profile; Female; Gene Expression Profiling - methods; Gene Expression Profiling - standards; Gene Expression Regulation, Neoplastic; Hepatitis E - complications; Hepatitis E - genetics; Hepatocellular carcinoma; Human viral diseases; Humans; IGFBP3; Infectious diseases; Liver Neoplasms - genetics; Liver Neoplasms - virology; Male; Medical sciences; Middle Aged; Polymerase Chain Reaction; Reproducibility of Results; Viral diseases; Viral hepatitis; DNA microarray; Hepatocellular carcinoma; Expression profile; Cryptogenic cirrhosis; IGFBP3; Human; DNA chip; Hepatic disease; Malignant tumor; Gene expression; Profile; Infection; Viral hepatitis B; Polymerase chain reaction; Viral disease; Digestive diseases; Molecular biology; Viral hepatitis C
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(03)00473-2

Background/Aims: Hepatocellular carcinoma (HCC) usually develops following chronic liver inflammation caused by hepatitis C or B virus. Through expression profiling in a rare type of HCC, for which the causes are unknown, we sought to find key genes responsible for each step of hepatocarcinogenesis in the absence of viral influence.
Methods: We used 68 non-B, non-C liver tissues (20 HCC, 17 non-tumor, 31 normal liver) for expression profiling with PCR-array carrying 3072 genes known to be expressed in liver tissues. To select the differentially expressed genes, we performed random permutation testing. A weighted voting classification algorithm was used to confirm the reliability of gene selection. We then compared these genes with the results of previous expression profiling studies.
Results: A total of 220 differentially expressed genes were selected by random permutation tests. The classification accuracies using these genes were 91.8, 92.0 and 100.0% by a leave-one-out cross-validation, an additional PCR-array dataset and a Stanford DNA microarray dataset, respectively. By comparing our results with previous reports on virus-infected HCC, four genes (ALB, A2M, ECHS1 and IGFBP3) were commonly selected in some studies.
Conclusions: The 220 differentially expressed genes selected by PCR-array are potentially responsible for hepatocarcinogenesis in the absence of viral influence.