Downregulation of RFX1 predicts poor prognosis of patients with small hepatocellular carcinoma

Objective: Regulatory factor X1 (RFX1) deletion has been reported to be correlated with poor prognosis of some types of cancer. The present study aimed to investigate the prognostic value of RFXI in HCC, especially in small hepatocellular carcinoma. Methods: Immunohistochemical assay was used to investigate RFXI expression in 221 HCC tissues and another validation cohort of 71 small HCC samples. We also performed in vitro experiments to investigate if RFX1 regulated invasive capacity of HCC cells and expression of epithelial-mesenchymal transition (EMT) markers. Results: We found that RFX1 expression was significantly lower in HCC tissues compared to the corresponding non-tumor tissues. Further survival analysis suggested that the downregulation of RFX1 correlated with poor prognosis and a high recurrence risk in HCC patients, particularly in small HCC patients. Furthermore, another validation cohort of small HCC samples confirmed that downregulation of RFXI in HCC tissues predicted high recurrence risk and poor prognosis for early stage HCC patients. In vitro studies suggested that knocking down RFX1 facilitated HCC cell invasion, while overexpression of RFXI reduced the invasion of HCC cells. Western blot assays also indicated that RFX1 regulated expression of some EMT markers. Knocking down RFXI decreased E-cadherin and increased vimentin expression, while RFXI overexpression enhanced E-cadherin and decreased vimentin expression. Conclusions: Our study demonstrated that RFXI downregulation is a new predictive marker of high recurrence risk and poor prognosis of HCC; It has potential to help guide treatment for postoperative HCC patients, especially for small HCC patients. (C) 2018 Published by Elsevier Ltd.