Table S1. The gene list of potential biomarkers. Table S2. Clinical characteristics of three bathes of HCC patients from Shanghai cohort. Table S3. Performance of candidate genes to predict HCC metastasis in leave-one-out cross-validation. Table S4. Expression patterns of candidate genes in three bathes of EHBH-Sh samples. Table S5. Univariate analysis of potential biomarkers using logistic regression in 57 Sh-PCR HCC samples. Table S6. The validation of metastasis model using leave-one-gene-out method. Table S7. Univariate Cox analysis of the probability of HCC metastasis and clinicopathological variables.
Funding
National “863” project of China
National “973” project of China
NSFC
National Natural Science Foundation of China
ARTICLE ABSTRACT
Purpose: The dismal outcome of hepatocellular carcinoma (HCC) is largely attributed to its early recurrence and venous metastases. We aimed to develop a metastasis-related model to predict hepatocellular carcinoma prognosis.Experimental Design: Using microarrays, sequencing, and RT-PCR, we measured the expression of mRNAs and lncRNAs in a training set of 94 well-defined low-risk (LRM) and high-risk metastatic (HRM) HCC patients from a Shanghai cohort. We refined a metastasis signature and established a corresponding model using logistic regression analysis. The validation set consisted of 567 HCC patients from four-center cohorts. Survival analysis was performed according to the metastasis model.Results: Using relative expression of tumor to para-tumor tissues, we refined the metastasis signature of five mRNAs and one lncRNA. A generalized linear model was further established to predict the probability of metastasis (MP). Using MP cutoff of 0.7 to separate LRM and HRM in Shanghai cohort, the specificity and sensitivity of the model were 96% [95% confidence interval (CI), 85%–99%] and 74% (95% CI, 58%–86%), respectively. Furthermore, HRM patients showed a significantly shorter overall and recurrence-free survival in validation cohorts (P < 0.05 for each cohort). Early HCC patients also have a poorer outcome for multicenter HRM patients. Finally, Cox regression analysis indicated that continuous MP was an independent risk factor and associated with the recurrence and survival of HCC patients after resection (HR 2.98–16.6, P < 0.05).Conclusions: We developed an applicable six-gene metastasis signature, which is robust and reproducible in multicenter cohorts for HCC prognosis. Clin Cancer Res; 23(1); 289–97. ©2016 AACR.
