Epidermal growth factor-like repeats and discoidin I-like domains 3: a multifaceted oncoprotein at the crossroad of MAPK and TGF-beta pathways in human hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a frequent human cancer with 0.25–1 million of newly diagnosed cases each year (1-3). Major risk factors associated with the development of HCC are chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, alcoholic hepatitis, aflatoxin B1 (3-5), and some inherited diseases (6). HCC is a fatal disease, with a life expectancy of about 6 months from the time of diagnosis (6). Early liver lesions could be detected by ultrasonography and efficiently treated by resection or radiofrequency ablation (7). However, only a minority of cases is eligible to these treatment modalities due to the late diagnosis of the disease (2,7,8). In addition, therapies with pharmacological agents or alternative approaches, including percutaneous ethanol injection, trans-arterial chemo-embolization or yttrium-90 microspheres, do not improve significantly the prognosis of patients with advanced disease (2,7,8).