title: A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients.
abstract: Metastasis-related recurrence often occurs in hepatocellular carcinoma (HCC) patients who receive curative therapies. At present, it is challenging to identify patients with high risk of recurrence, which would warrant additional therapies. In this study, we sought to analyze a recently developed metastasis-related gene signature for its utility in predicting HCC survival, using 2 independent cohorts consisting of a total of 386 patients who received radical resection. Cohort 1 contained 247 predominantly HBV-positive cases analyzed with an Affymetrix platform, whereas cohort 2 contained 139 cases with mixed etiology analyzed with the NCI Oligo Set microarray platform. We employed a survival risk prediction algorithm with training, test, and independent cross-validation strategies and found that the gene signature is predictive of overall and disease-free survival. Importantly, risk was significantly predicted independently of clinical characteristics and microarray platform. In addition, survival prediction was successful in patients with early disease, such as small (<5 cm in diameter) and solitary tumors, and the signature predicted particularly well for early recurrence risk (<2 years), especially when combined with serum alpha fetoprotein or tumor staging. In conclusion, we have shown in 2 independent cohorts with mixed etiologies and ethnicity that the metastasis gene signature is a useful tool to predict HCC outcome, suggesting the general utility of this classifier. We recommend the use of this classifier as a molecular diagnostic test to assess the risk that an HCC patient will develop tumor relapse within 2 years after surgical resection, particularly for those with early-stage tumors and solitary presentation.
authors.affiliation: Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Roessler
authors.forename: Hu-Liang
authors.initials: HL
authors.lastname: Jia
authors.forename: Anuradha
authors.initials: A
authors.lastname: Budhu
authors.forename: Marshonna
authors.initials: M
authors.lastname: Forgues
authors.forename: Qing-Hai
authors.initials: QH
authors.lastname: Ye
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.forename: Snorri S
authors.initials: SS
authors.lastname: Thorgeirsson
authors.forename: Zhongtang
authors.initials: Z
authors.lastname: Sun
authors.forename: Zhao-You
authors.initials: ZY
authors.lastname: Tang
authors.forename: Lun-Xiu
authors.initials: LX
authors.lastname: Qin
authors.forename: Xin Wei
authors.initials: XW
authors.lastname: Wang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D015331:Cohort Studies; D015870:Gene Expression; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology*; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity