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

Mima,Kosuke; Hayashi,Hiromitsu; Kuroki,Hideyuki; Nakagawa,Shigeki; Okabe,Hirohisa; Chikamoto,Akira; Watanabe,Masayuki; Beppu,Toru; Baba,Hideo

doi:10.3892/ol.2012.954

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

Authors:
- Kosuke Mima
- Hiromitsu Hayashi
- Hideyuki Kuroki
- Shigeki Nakagawa
- Hirohisa Okabe
- Akira Chikamoto
- Masayuki Watanabe
- Toru Beppu
- Hideo Baba
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Affiliations: Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
Published online on: October 5, 2012 https://doi.org/10.3892/ol.2012.954
Pages: 149-154

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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.

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