Abstract
A previous study demonstrated that cytokeratin 19 (CK19) expression in hepatocellular carcinoma (HCC) is an indicator of HCC invasiveness, including lymph node metastasis (LNM), tumor infiltration/non-encapsulation and poor prognosis. The exact mechanism by which CK19 expression results in poor prognosis remains unclear. Through the use of an Affymetrix U133A oligonucleotide microarray [20 patients with hepatitis B virus (HBV)-HCC], it was demonstrated that cadherin 17 (CDH17) significantly correlated with CK19 expression (R2, 0.867; P<0.001) in HBV-HCC. Immunohistochemical analysis (114 patients with HBV-HCC) also demonstrated a significant correlation between CK19 and CDH17 expressions in primary tumor tissue (R2, 0.414; P<0.001). In addition, CK19 and CDH17 expressions levels revealed a significant association with LNM (P<0.001). Cox regression multivariate analysis demonstrated that indocyanine green retention at 15 min >10% and CDH17 expression were independent prognostic factors for disease free survival (P=0.010 and 0.002, respectively). In vitro studies showed that epidermal growth factor can induce the expression of both CK19 and CDH17, and CDH17 in turn can enhance the expression of CK19 in HCC. In summary, this study demonstrated that the early recurrence and poor prognosis of CK19(+) HCC may be due to the expression of CDH17, a gene known to be associated with vascular invasion, tumor metastasis, and advanced tumor stage of HCC. Thus, novel therapeutics by targeting CDH17 may be beneficial for CK19(+) HCC.