Prognostic value of multiple epithelial mesenchymal transition-associated proteins in intrahepatic cholangiocarcinoma.

The aim of the present study was to investigate the expression of epithelial mesenchymal transition (EMT)-associated proteins and their prognostic value in intrahepatic cholangiocarcinoma (ICC). The expression of six EMT-associated proteins, including E-cadherin, N-cadherin, Vimentin, Snail family transcriptional repressor 1 (Snail), Snail family transcriptional repressor 2 (Slug) and S100 calcium binding protein A4 (S100A4) was determined by immunohistochemistry in 109 patients with ICC who had received surgery. Survival analysis showed that patients with low E-cadherin expression (P<0.001) or high S100A4 (P<0.001) or Snail (P<0.001) expression had a reduced survival time. Based on the numbers of alterations in the expression of EMT-associated proteins as determined by immunohistochemical analysis, the patients were categorized as low (score, 0-3; n=75) or high (score, ≥4; n=34) EMT expression groups. The high EMT expression group was significantly associated with positive lymph node metastasis (P=0.023) and late Tumor-Node-Metastasis (TNM) stage (P<0.001). Furthermore, patients in the high EMT expression group had a significantly poorer overall survival time than those in the low EMT expression group (P<0.001). Multivariate analysis indicated that EMT status was a significant independent predictor for overall survival time (P=0.004), and was linked to surgical margin (P=0.013) and TNM stage (P<0.001). In conclusion, the reduced expression of E-cadherin and high expression of Snail and S100A4 were significantly associated with the poor survival of patients with ICC after surgery. The EMT protein expression status was associated with ICC progression, and may be considered as an independent prognostic indicator for patients with ICC.