Our findings collectively indicate that Notch receptors variants (rs1043996 in Notch3 and rs422951, rs520692, rs3830041 in Notch4) are independent predictive targets for OS in HBV-related HCC patients.
In summary, the present study demonstrated that Notch1, Notch3 and Notch4 were upregulated in HCC tissues and that HBx and HIF-1α may be the factors that cause the overexpression of Notch genes.
The present study indicates that HBx activates Notch signaling by its effects on Notch1 and Notch4, and therefore, recruits Notch signaling as a downstream pathway contributing to its carcinogenic role in HBV-associated HCC.
Cytoplasmic and nuclear Notch1 was detected in 88.7% (47/53) and 9.4% (5/53) of hepatocellular carcinoma tissues, respectively; positive rates of Notch4 were 67.9% (36/53) in cytoplasm and 52.8% (31/53) in nucleus.
Compared with adjacent nontumour liver, Notch1 (cytoplasmic) and Notch4 (nuclear) were up-regulated (P<0.05, P<0.05), Notch2 was down-regulated (P<0.05), while Notch1 (nuclear), Notch3 and Notch4 (cytoplasmic) showed no difference between hepatocellular carcinoma and adjacent nontumour liver.