Molecular signatures and prognosis of hepatocellular carcinoma

Prognostic prediction is a vital component in clinical management of hepatocellular carcinoma (HCC) patients. Rapidly evolving genomic assays serve as flexible sources to discover molecular signatures that sensitively and specifically predict clinical outcome of the patients. Studies have identified molecular signatures of HCC tumors that depict biological aggressiveness yielded through activation of specific genes and molecular pathways such as MYC, AKT, TGF-beta, and IGF2 as well as inactivation of TP53 pathway. Despite the promise for tumor-derived signatures' role in therapeutic target discovery, their value as prognostic marker seems to be limited especially in early-stage HCC, which has been increasing as a result of successful implementation HCC surveillance for patients with liver cirrhosis. In contrast, non-tumor, diseased liver tissues turn out to be a rich source of molecular information to capture propensity to hepatocarcinogenesis and metastasis through dyregulation of growth signaling and inflammatory/oxidative stress/immune response. In addition, the liver-derived signatures hold prognostic relevance irrespective of HCC stage, suggesting their role as prognostic markers. Furthermore, they may also be utilized for development of HCC chemoprevention therapy.