Molecular-based prediction of early recurrence in hepatocellular carcinoma.
OBJECTIVE
Hepatocellular carcinoma (HCC) has a very poor prognosis, due to the high incidence of tumor recurrence. As the current morphological indicators are often insufficient for therapeutic decisions, we sought to identify additional biologic indicators for early recurrence.


METHODS
We analyzed gene expression using a PCR-based array of 3,072 genes in 100 HCC patients. Informative genes predicting early intrahepatic recurrence were selected by random permutation testing, and a weighted voting prediction method was constructed. Following estimation of prediction accuracy, a multivariate Cox analysis was performed.


RESULTS
By permutation testing, we selected 92 genes demonstrated distinct expression patterns differing significantly between recurrence cases and recurrence-free cases. Our prediction method, using the 20 top-ranked genes, correctly predicted the early intrahepatic recurrence for 29 of 40 cases within the validation group, and the odds ratio was 6.8 (95%CI 1.7-27.5, P = 0.010). The 2-year recurrence rates in the patients with the good signature and those with the poor signature were 29.4 and 73.9%, respectively. Multivariate Cox analysis revealed that molecular-signature was an independent indicator for recurrence (hazard ratio 3.82, 95%CI 1.44-10.10, P = 0.007).


CONCLUSIONS
Our molecular-based prediction method using 20 genes is clinically useful to predict early recurrence of HCC.
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka Univeristy, Suita city, Osaka 565-0871, Japan.
Yukinori
Y
Kurokawa
Ryo
R
Matoba
Ichiro
I
Takemasa
Hiroaki
H
Nagano
Keizo
K
Dono
Shoji
S
Nakamori
Koji
K
Umeshita
Masato
M
Sakon
Noriko
N
Ueno
Shigeyuki
S
Oba
Shin
S
Ishii
Kikuya
K
Kato
Morito
M
Monden
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models