Vascular endothelial growth factor is associated with hepatocellular carcinoma recurrence, independent of folate and glutathione-related antioxidant enzymes: A follow-up study.

• Folate and glutathione (GSH) increased after tumor resection in hepatocellular carcinoma (HCC). • Vascular endothelial growth factor (VEGF) showed a decreased trend during follow-up in HCC. • VEGF correlates with folate, GSH, and GSH-related antioxidant enzymes in HCC. • The pre-resection VEGF level is a potential independent marker to predict HCC recurrence. The associations of tumor angiogenesis with folate and antioxidant capacities in patients with hepatocellular carcinoma (HCC) and their effects on HCC recurrence have not yet been investigated. We investigated the changes and relationships of VEGF, folate, GSH, and GSH-related antioxidant enzymes in patients with HCC before tumor resection, as well as 1 month, 1 year, and 3 years after tumor resection, and their effects on HCC recurrence. 95 HCC patients who underwent tumor resection were recruited. Patients were followed up before tumor resection (pre-resection), 1 month after tumor resection (post-resection), 1 year, and 3 years of follow-up. The recurrence and survival status of patients were evaluated. Plasma VEGF concentrations decreased slightly during follow-up. Serum folate and GSH concentrations and plasma GPx and GR activities increased significantly from pre-resection to post-resection and remained stable at follow-up. Pre-resection plasma VEGF was positively correlated with GSH, GPx, and GR, but negatively correlated with folate and GST. The high pre-resection plasma VEGF was a significant predictor of a high HCC rate (hazard ratio = 1.05, p = 0.035), remaining significant after adjustments for folate, GSH, GPx, GR, and GST to diminish their interference with VEGF. Pre-tumor-resection plasma VEGF constitutes a potential independent marker for predicting HCC recurrence. However, the associations of plasma VEGF with folate and GSH-related antioxidant capacities in HCC patients cannot be ignored. This study followed 95 patients with HCC who underwent tumor resection. VEGF decreased slightly during follow-up. Folate, GSH, GPx, and GR increased significantly after tumor resection and remained steady. Pre-resection VEGF correlated with folate, GSH, GPx, and GR. High pre-resection VEGF levels independently predicted a high HCC recurrence rate. HCC, hepatocellular carcinoma; VEGF, vascular endothelial growth factor; GSH, glutathione; GPx, glutathione peroxidase; GR, glutathione reductase. [Display omitted] [ABSTRACT FROM AUTHOR]