Molecular profiling of liver tumors: classification and clinical translation for decision making

Abstract

Hepatocellular carcinoma (HCC) is a complex disease with a dismal prognosis. Consequently, a translational approach is required to personalized clinical decision making to improve survival of HCC patients. Molecular signatures from cirrhotic livers and single nucleotide polymorphism have been linked with HCC occurrence. Identification of high-risk populations will be useful to design chemopreventive trials. In addition, molecular signatures derived from tumor and nontumor samples are associated with early tumor recurrence due to metastasis and late tumor recurrence due to de novo carcinogenesis after curative treatment, respectively. Identification of patients with a high risk of relapse will guide adjuvant randomized trials. The genetic landscape drawn by next-generation sequencing has highlighted the genomic diversity of HCC. Genetic drivers recurrently mutated belong to different signaling pathways including telomere maintenance, cell-cycle regulators, chromatin remodeling, Wnt/b-catenin, RAS/RAF/MAPK kinase, and AKT/mTOR pathway. These cancer genes will be ideally targeted by biotherapies as a paradigm of stratified medicine adapted to tumor biology.

Fig. 1

Potential translation of molecular knowledge of hepatocellular carcinoma (HCC) in clinical practice. Potential uses of genetic and molecular knowledge in the prediction of HCC development in patients with cirrhosis, in HCC diagnosis, prognosis assessment, and stratification of targeted therapy according to the genetic defect of the tumor. It aims to develop tailored chemopreventive trial, targeted treatment of high risk preneoplastic lesions, stratified adjuvant therapies after curative treatment, and biomarker-driven randomized trial in advanced stages.