A three-gene predictor for early intrahepatic recurrence of hepatocellular carcinoma after curative hepatectomy.
We previously developed a DNA microarray-based system that out-performs traditionally used clinical parameters for prediction of early intrahepatic recurrence (IHR) of hepatocellular carcinoma (HCC). Because DNA microarray is too expensive for daily clinical use, we used a quantitative real-time reverse transcription-polymerase chain reaction (QRT-PCR) to develop a lower-cost predictor for early IHR. From the 12 early IHR-related genes integrated in the previous predictor, we selected 6 genes whose levels showed the strongest association between data from the 2 distinct DNA microarray platforms with the same sample set. Expression of these 6 genes relative to that of GAPDH was measured by QRT-PCR in 82 HCCs. Of the 82 HCCs, 39 and 43 were assigned to training and independent test sets, respectively. By searching all combinations (n=2-6) of the 6 genes, we found an optimal combination of 3 genes (HLADRA, DDX17 and LAPTM5) that minimized the leave-one-out error for prediction of early IHR in the training set. The 3-gene predictor constructed with the Fisher linear classifier correctly predicted early IHR or non-recurrence in 35 (81.4%) of 43 HCCs in the independent test set and had a high positive predictive value of 72.7% and a high negative predictive value of 84.4%. Multivariate analysis with the stepwise logistic regression showed that the 3-gene predictor [F(x)<0] was an independent risk factor for early IHR (risk ratio, 13.6; p=0.006), indicating its potential as an easy-to-use predictor for accurate prediction of early IHR of HCC.
Somura
Hideaki
H
Department of Surgery II, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, Japan.
Iizuka
Norio
N
Tamesa
Takao
T
Sakamoto
Kazuhiko
K
Hamaguchi
Takashi
T
Tsunedomi
Ryouichi
R
Yamada-Okabe
Hisafumi
H
Sawamura
Mikiko
M
Eramoto
Masaya
M
Miyamoto
Takanobu
T
Hamamoto
Yoshihiko
Y
Oka
Masaaki
M
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000601:surgery*; D053487:DEAD-box RNA Helicases / Q000235:genetics; D042241:Early Diagnosis; D005260:Female; D015870:Gene Expression; D052138:Genes, Neoplasm; D006684:HLA-DR Antigens / Q000235:genetics; D006498:Hepatectomy; D006801:Humans; D008113:Liver Neoplasms / Q000601:surgery*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods*
D014408:Biomarkers, Tumor; D006684:HLA-DR Antigens; D008565:Membrane Proteins; D012333:RNA, Messenger; C100848:LAPTM5 protein, human; C102004:DDX17 protein, human; D053487:DEAD-box RNA Helicases