Gene expression-based recurrence prediction of hepatitis B virus-related human hepatocellular carcinoma.
OBJECTIVE
The poor prognosis of hepatocellular carcinoma (HCC) is, in part, due to the high rate of recurrence even after "curative resection" of tumors. Therefore, it is axiomatic that the development of an effective prognostic prediction model for HCC recurrence after surgery would, at minimum, help to identify in advance those who would most benefit from the treatment, and at best, provide new therapeutic strategies for patients with a high risk of early recurrence.


METHODS
For the prediction of the recurrence time in patients with HCC, gene expression profiles were generated in 65 HCC patients with hepatitis B infections.


RESULTS
Recurrence-associated gene expression signatures successfully discriminated between patients at high-risk and low-risk of early recurrence (P=1.9 x 10(-6), log-rank test). To test the consistency and robustness of the recurrence signature, we validated its prognostic power in an independent HCC microarray data set. CD24 was identified as a putative biomarker for the prediction of early recurrence. Genetic network analysis suggested that SP1 and peroxisome proliferator-activated receptor-alpha might have regulatory roles for the early recurrence of HCC.


CONCLUSIONS
We have identified a gene expression signature that effectively predicted early recurrence of HCC independent of microarray platforms and cohorts, and provided novel biological insights into the mechanisms of tumor recurrence.
Woo
Hyun Goo
HG
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Park
Eun Sung
ES
Cheon
Jae Hee
JH
Kim
Ju Han
JH
Lee
Ju-Seog
JS
Park
Bum Joon
BJ
Kim
Won
W
Park
Su Cheol
SC
Chung
Young Jin
YJ
Kim
Byeong Gwan
BG
Yoon
Jung-Hwan
JH
Lee
Hyo-Suk
HS
Kim
Chung Yong
CY
Yi
Nam-Joon
NJ
Suh
Kyung-Suk
KS
Lee
Kuhn Uk
KU
Chu
In-Sun
IS
Roskams
Tania
T
Thorgeirsson
Snorri S
SS
Kim
Yoon Jun
YJ
D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D015870:Gene Expression; D020869:Gene Expression Profiling; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic / Q000150:complications / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis
D014408:Biomarkers, Tumor