Twist Expression in Circulating Hepatocellular Carcinoma Cells Predicts Metastasis and Prognoses

Hepatocellular carcinoma (HCC) is one of the leading malignancies worldwide. Enumeration of circulating tumor cells (CTCs) has been demonstrated to be a prognostic indicator in HCC. Twist plays a critical role in metastasis and has been proposed as a biomarker for epithelial-mesenchymal transition (EMT). However, links between the expression of Twist in CTCs and HCC clinical parameters are still unclear. This study aims to evaluate the relationship between Twist expression in CTCs and clinicohistopathological risk factors of HCC. Between June 2015 and July 2017, 80 HCC patients and 10 healthy volunteers were enrolled in this study. CTCs were isolated and analyzed by the optimized CanPatrol™ CTC-enrichment technique. Our analysis showed that Twist+ CTCs were detected in 54 of the 80 (67.5%) HCC patients. The positive ratios of Twist+ CTCs correlated with portal vein tumor thrombi, TNM staging, AFP, cirrhosis, tumor number, tumor size, and microvascular invasion. Meanwhile, the follow-up results of the 33 HCC patients who underwent hepatectomy showed that the positive ratios of Twist+ CTCs were closely correlated with the rate of metastasis or recurrence and the mortality rate. The ROC curve analyses suggested that the prognostic evaluation of Twist+ CTCs outperforms CTCs alone. Twist+ CTCs showed higher expression in Glypican-3 protein. In conclusion, Twist expression in CTCs could serve as a biomarker for evaluating HCC metastasis and prognosis.