HGFAC expression decreased in liver cancer and its low expression correlated with DNA hypermethylation and poor prognosis

Abstract As the activator of hepatocyte growth factor (HGF), hepatocyte growth factor activator (HGFAC) has been previously reported to involve in liver, kidney, and stomach regeneration in response to injury and several types of cancers. This study aimed to explore the expression of HGFAC and the correlation between decreased HGFAC and DNA methylation in liver cancer and its clinical significance. The molecular profiling of HGFAC in liver cancer was analyzed using genomic, transcriptomic, immunohistochemistry, and patient survival information from databases, including oncomine, HPA, COSMIC, UCSC Xena, MPRESS, and Kaplan‐Meier plotter. It was found that HGFAC expression at transcriptional and translational level decreased in liver cancer compared with normal tissues. There is a negative correlation between the HGFAC expression and methylation around the promoter region which indicated that HGFAC expression might be controlled by DNA methylation. Moreover, the decreased HGFAC is associated with significantly short over survival time in liver cancer patients. In conclusion, decreased HGFAC expression in liver cancer associated with poor survival outcome. Hypermethylation around the promoter region contributed to the decreased expression of HGFAC. HGFAC may be a useful and predictive biomarker for the prognosis of liver cancer patients. To the best of our knowledge, this is the first report describing the relationship between HGFAC DNA methylation and its expression.