The role of Twist1 in hepatocellular carcinoma angiogenesis: a clinical study

The epithelial-mesenchymal transition regulator Twist1 has been implicated in tumor invasion, metastasis, and vasculogenic mimicry formation of human hepatocellular carcinoma. However, the relationship between Twist1 expression and endothelium-dependent angiogenesis is not clear. In this study, to investigate the role of Twist1 in hepatocellular carcinoma angiogenesis, we measured the microvessel density by CD31 immunohistochemistry stain and explored the microvessel density as an angiogenesis indicator. The microvessel density in paraffin sections from 97 patients was correlated with Twist1 expression up-regulation. Nuclear relocation was also identified based on immunohistochemistry stain, presenting a significant clinical pattern in hepatocellular carcinoma metastasis and prognosis. Twist1 expression, which is both located in the cytoplasm and relocated into the nucleus, was associated with matrix metalloproteinase 9 up-regulation; matrix metalloproteinase 2 did not appear to present these effects in hepatocellular carcinoma. An assessment of microvessel density could provide an estimate of the degree of angiogenic activity in tissues, as well as its association with Twist1 up-regulated expression. To the best of our knowledge, not only is Twist1 related to metastasis by tumor cells, but vasculogenic mimicry is also significantly related to microvessel density; this process is also associated with matrix metalloproteinase 9 up-regulated expression. This work provides a better understanding of the role of Twist1 in hepatocellular carcinoma angiogenesis and metastasis, suggesting that our findings could represent tumor cell epithelial-mesenchymal transition and endothelium-dependent angiogenesis, as can be seen in hepatocellular carcinoma.