Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma: Clinical significance of transforming growth factor-β signaling

Abstract

Epithelial-mesenchymal transition (EMT) plays a pivotal role in cancer invasion and metastasis, and transforming growth factor (TGF)-β signaling is a potent inducer of EMT. However, the clinical significance of the correlation between EMT marker expression and TGF-β signaling in hepatocellular carcinoma (HCC) patients remains unknown. In this study, immunohistochemistry was used to analyze the expression of EMT markers and phospho-Smad2 nuclear positivity, and their association with clinicopathological features in 150 HCC patients. E-cadherinhigh/vimentinlow and E-cadherinlow/vimentinhigh expression profiles were determined in 55 (36.7%) and 21 (14.0%) patients, respectively. The E-cadherinlow/vimentinhigh expression profile was significantly correlated with poor tumor differentiation (P<0.001), vascular invasion (P=0.007) and extrahepatic recurrence following curative surgery (P=0.026). Furthermore, the E-cadherinlow/vimentinhigh expression profile was significantly correlated with shorter disease-free survival compared to E-cadherinhigh/vimentinlow (P=0.002). Forty-one patients (27.3%) were demonstrated to have high phospho-Smad2 nuclear positivity, which was significantly correlated with the E-cadherinlow/vimentinhigh expression profile (P<0.001). In conclusion, this study suggests that EMT expression profiles are useful prognostic markers for disease-free survival in HCC patients, and that the E-cadherinlow/vimentinhigh expression profile is closely associated with high-grade malignant behavior such as tumoral vascular invasion and metastasis in HCC. Additionally, TGF-β-mediated EMT may play an important role in the aggressiveness of HCC.