A Unique Metastasis Gene Signature Enables Prediction of Tumor Relapse in Early-Stage Hepatocellular Carcinoma Patients

作者：Stéphanie Roessler, Hu-Liang Jia, Anuradha Budhu, Marshonna Forgues, Qing-Hai Ye, Ju‐Seog Lee, Snorri S. Thorgeirsson, Zhongtang Sun, Zhao-You Tang, Lun‐Xiu Qin, Xin Wei Wang · 发表于：Cancer Research · 年份：2010 · DOI：10.1158/0008-5472.can-10-2607 · 被引用次数：1106 · 研究领域：Hepatocellular Carcinoma Treatment and Prognosis、Cholangiocarcinoma and Gallbladder Cancer Studies、Ferroptosis and cancer prognosis

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. W...