Although it is interesting to selleck kinase inhibitor see that risk score reflects biological characteristics (Supporting Table 4), its associations need to be validated in future studies. For example, activation of AKT is the most commonly altered signaling event in many cancers and many genetic alterations lead to activation of AKT.32 Thus, it is currently uncertain whether AKT is

the driver of tumor development in patients with a high risk score and would be potential therapeutic targets for these patients. However, the significant association of risk score with CTNNB1 mutations is in good agreement with the results of previous studies demonstrating a significant correlation between CTNNB1 mutations and a favorable prognosis among patients with HCC.33, 34 Moreover, TBX3, one of the canonical downstream target genes of CTNNB1,35 was included in our 65-gene signature, and its expression was associated with a better prognosis, which strongly supports the activation of CTNNB1 in the low-risk group in all HCC patients examined. It is also noteworthy that the risk score does not reflect the status of underlying liver disease, indicating that there might be room for improvement. A previous study identified a prognostic gene expression signature from surrounding nontumor tissues

of patients with HCC that better reflects biological characteristics learn more SSR128129E of underlying liver disease than tumors.12 The risk score might be improved by incorporating genomic data from surrounding tissues that does not overlap with but is complementary to those from tumor tissues. Classification of human cancers into more homogenous clinical groups such as stages and grades significantly improved the

treatment of patients by standardizing patient care. Molecular classification of cancers further improved patient care by enabling the development of treatments tailored to the abnormalities present in each patient’s cancer cells. Currently, decision-making for HCC treatment in the clinical setting is mainly based on clinical data, which is best reflected in BCLC staging and its associated treatment algorithm.2 However, this staging method offers little or almost no information about biological characteristics of HCC that would be very critical for tailored treatment in the future. Importantly, risk score may provide clues on biological characteristics of tumors (i.e., activation of CTNNB1) as well as prognostic characteristics. Thus, it would provide an opportunity for developing rationalized clinical trials based on the molecular characteristics of tumors that are supplemental to current staging systems. Because our data showed that a small number of genes (65 genes) is sufficient to identify patient with a poor prognosis (Supporting Fig.