Oligonucleotide microarray for prediction of early intrahepatic recurrence of hepatocellular carcinoma after curative resection.
BACKGROUND
Hepatocellular carcinoma has a poor prognosis because of the high intrahepatic recurrence rate. There are technological limitations to traditional methods such as TNM staging for accurate prediction of recurrence, suggesting that new techniques are needed.


METHODS
We investigated mRNA expression profiles in tissue specimens from a training set, comprising 33 patients with hepatocellular carcinoma, with high-density oligonucleotide microarrays representing about 6000 genes. We used this training set in a supervised learning manner to construct a predictive system, consisting of 12 genes, with the Fisher linear classifier. We then compared the predictive performance of our system with that of a predictive system with a support vector machine (SVM-based system) on a blinded set of samples from 27 newly enrolled patients.


RESULTS
Early intrahepatic recurrence within 1 year after curative surgery occurred in 12 (36%) and eight (30%) patients in the training and blinded sets, respectively. Our system correctly predicted early intrahepatic recurrence or non-recurrence in 25 (93%) of 27 samples in the blinded set and had a positive predictive value of 88% and a negative predictive value of 95%. By contrast, the SVM-based system predicted early intrahepatic recurrence or non-recurrence correctly in only 16 (60%) individuals in the blinded set, and the result yielded a positive predictive value of only 38% and a negative predictive value of 79%.


CONCLUSIONS
Our system predicted early intrahepatic recurrence or non-recurrence for patients with hepatocellular carcinoma much more accurately than the SVM-based system, suggesting that our system could serve as a new method for characterising the metastatic potential of hepatocellular carcinoma.
Iizuka
Norio
N
Department of Bioregulatory Function, Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan.
Oka
Masaaki
M
Yamada-Okabe
Hisafumi
H
Nishida
Minekatsu
M
Maeda
Yoshitaka
Y
Mori
Naohide
N
Takao
Takashi
T
Tamesa
Takao
T
Tangoku
Akira
A
Tabuchi
Hisahiro
H
Hamada
Kenji
K
Nakayama
Hironobu
H
Ishitsuka
Hideo
H
Miyamoto
Takanobu
T
Hirabayashi
Akira
A
Uchimura
Shunji
S
Hamamoto
Yoshihiko
Y
D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011237:Predictive Value of Tests