Published online Oct 27, 2018. doi: 10.4254/wjh.v10.i10.645
Peer-review started: April 21, 2018
First decision: May 8, 2018
Revised: June 8, 2018
Accepted: June 27, 2018
Article in press: June 28, 2018
Published online: October 27, 2018
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide and the second leading cause of death among all cancer types. Deregulation of the networks of tissue-specific transcription factors (TFs) observed in HCC leads to profound changes in the hepatic transcriptional program that facilitates tumor progression. In addition, recent reports suggest that substantial aberrations in the production of TF isoforms occur in HCC. In vitro experiments have identified distinct isoform-specific regulatory functions and related biological effects of liver-specific TFs that are implicated in carcinogenesis, which may be relevant for tumor progression and clinical outcome. This study reviews available data on the expression of isoforms of liver-specific and ubiquitous TFs in the liver and HCC and their effects, including HNF4α, C/EBPs, p73 and TCF7L2, and indicates that assessment of the ratio of isoforms and targeting specific TF variants may be beneficial for the prognosis and treatment of HCC.
Core tip: This paper aims to analyze existing data on the spectrum of isoforms of liver-specific transcription factors produced in the liver and hepatocellular carcinoma (HCC) and implicated in carcinogenesis, their distinct regulatory functions and subsequent isoform-dependent biological effects which may be relevant for tumor progression and clinical outcomes in HCC patients.