期刊
SCIENTIFIC REPORTS
卷 9, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-019-45537-w
关键词
-
资金
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2019R1A2C1009439]
To date, few studies have carried out a simultaneous determination of multiple pro-and anti-angiogenic factors during liver diseases progression. This study investigated the dynamic change in circulating angiogenic factors in multi-step carcinogenesis and hepatocellular carcinoma (HCC) progression. Serum levels of major pro-angiogenic [Vascular endothelial growth factor (VEGF), Basic fibroblast growth factor (b-FGF)] and anti-angiogenic [Thrombospondin-1 (TSP-1), Endostatin] factors were identified by enzyme-linked immunosorbent assay and correlated with liver diseases progression and outcomes of HCC patients undergoing transarterial chemo-embolization. A total of 240 patients (156 HCC, 37 cirrhosis and 47 chronic hepatitis) were enrolled in this study. While progressing from chronic hepatitis, cirrhosis to HCC, VEGF and b-FGF levels showed a significant change. Particularly, b-FGF yielded the highest AUROC value for a diagnosis of HCC and its distinction from other disease groups. A trend towards increasing VEGF levels was observed from Child-Pugh class A, B to C. VEGF and TSP-1 levels increased with the advance of cancer stage, with a remarkable increase in TSP-1 at an intermediate stage. Pretreatment levels of VEGF, TSP-1, and endostatin independently predicted the overall survival of patients. VEGF and TSP-1 levels correlated with progression-free survival. Our study demonstrated the dynamic angiogenic switch and the roles that individual pro-and anti-angiogenic factors contribute to carcinogenesis and HCC progression during the course of multi-step liver diseases. These imply the future possibility of testing pro-and anti-angiogenic panels as a diagnostic marker and a guide in decision-making about upcoming targeted therapies.
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