Coexpression of Bcl-2 with epithelial-mesenchymal transition regulators is a prognostic indicator in hepatocellular carcinoma.

The anti-apoptosis factor Bcl-2 is known to contribute to tumorigenesis and metastasis. Epithelial-mesenchymal transition (EMT) may also participate in tumor invasion and metastasis. This study investigated the relationship between coexpression profiles of Bcl-2 and EMT regulators in hepatocellular carcinoma (HCC) tumor samples and clinical outcome. The nuclear (Nu) and cytoplasmic (Cyt) expression of Bcl-2 and the EMT regulators Twist-1, Twist-2, and Snail were determined by immunohistochemical staining in tumor tissue isolated from 97 HCC patients. The clinical prognostic values of both individual protein expression and various expression combinations were investigated using univariate and multivariate survival analysis. Results showed that patients with nuclear expression of Bcl-2 had worse clinical outcomes than patients exhibiting cytoplasmic expression. Overall survival was significantly shorter in HCC patients individually expressing Bcl-2-Nu, Twist-1-Nu, Twist-1-Cyt, and Snail (all P<0.05). Patients coexpressing Bcl-2-Nu with Twist-1-Nu, Twist-1-Cyt, Twist-2, or Snail had even worse prognoses than those expressing no biomarker or any one biomarker alone (all P<0.05). Multivariate analysis showed that HCC patients coexpressing Bcl-2-Nu with Twist-1-Cyt had the worst prognosis. This study provides clinical evidence that nuclear expression of Bcl-2 combined with cytoplasmic expression of Twist-1 is a predictor of very poor prognosis in HCC. Coexpression profiles of Bcl-2 and EMT regulators might aid in the selection of the most efficacious therapy for patients with HCC.