Molecular features of non-B, non-C hepatocellular carcinoma: a PCR-array gene expression profiling study.
OBJECTIVE
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.
Kurokawa
Yukinori
Y
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita city, Osaka 565-0871, Japan.
Matoba
Ryo
R
Takemasa
Ichiro
I
Nakamori
Shoji
S
Tsujie
Masanori
M
Nagano
Hiroaki
H
Dono
Keizo
K
Umeshita
Koji
K
Sakon
Masato
M
Ueno
Noriko
N
Kita
Hiroko
H
Oba
Shigeyuki
S
Ishii
Shin
S
Kato
Kikuya
K
Monden
Morito
M
D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods* / Q000592:standards; D015972:Gene Expression Regulation, Neoplastic; D016751:Hepatitis E / Q000150:complications / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015203:Reproducibility of Results