Laboratory of Tropical Biomedicine and Biotechnology, School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, China.
Department of Clinical Laboratory, Tumor Hospital of Shaanxi Province, Affiliated to the Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
J Cell Biochem. 2019 Jun;120(6):9692-9699. doi: 10.1002/jcb.28247. Epub 2019 Jan 11.
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.
作为肝细胞生长因子 (HGF) 的激活剂，肝细胞生长因子激活剂 (HGFAC) 先前已被报道参与肝脏、肾脏和胃的再生，以响应损伤和几种类型的癌症。本研究旨在探索 HGFAC 在肝癌中的表达及其与 DNA 甲基化的相关性以及其临床意义。使用数据库中的基因组、转录组、免疫组织化学和患者生存信息，包括 oncomine、HPA、COSMIC、UCSC Xena、MPRESS 和 Kaplan-Meier plotter，分析了肝癌中 HGFAC 的分子谱。结果发现，与正常组织相比，肝癌中 HGFAC 的转录和翻译水平表达降低。HGFAC 表达与启动子区域周围的甲基化之间存在负相关，这表明 HGFAC 表达可能受 DNA 甲基化的控制。此外，HGFAC 的表达降低与肝癌患者的总生存期显著缩短有关。总之，肝癌中 HGFAC 表达降低与不良生存结局相关。启动子区域周围的高甲基化导致 HGFAC 表达降低。HGFAC 可能是预测肝癌患者预后的有用标志物。据我们所知，这是首次描述 HGFAC DNA 甲基化与其表达之间关系的报告。
