A -catenin-related transcriptional signature predicts survival outcomes in hepatocellular carcinoma patients.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer and a major cause of cancer-related deaths worldwide. Nevertheless, treatment and prognosis are still dependent on clinical and pathological factors, given that molecular biomarkers predicting survival outcomes are lacking. The extensive molecular heterogeneity characterizing HCC is denoted by the large number of signaling pathways involved in tumor initiation and progression. Among these, aberrant activation of the Wnt/-catenin pathway is the most frequent alteration. Various mechanisms can contribute to signaling hyperactivation, including somatic mutations and epigenetic alterations. Here, we have identified a Wnt/-catenin-related transcriptional signature denoting hyperactivated pathway signaling regardless of the presence of pathway-related activating mutations. The WNT signature predicts survival outcomes in two independent HCC patient cohorts and is associated with distinctive immunogenomic features denoting immune exclusion.