Impact of serum vascular endothelial growth factor on prognosis in patients with unresectable hepatocellular carcinoma after transarterial chemoembolization

Abstract

Objective: To investigate the expression level of serum vascular endothelial growth factor (VEGF) in patients with unresectable hepatocellular carcinoma (HCC) and its relationship with the clinicopathological characteristics, and to assess the impact of serum VEGF as a predictive factor for HCC prognosis during transarterial chemoembolization (TACE) treatments.Methods: Serum VEGF levels were measured using enzyme-linked immunosorbent assay (ELISA) in 60 random patients who underwent TACE or transarterial infusion (TAI) for unresectable HCC between May and September 2008 and 12 healthy volunteers were also involved in this study to serve as control. All patients' clinicopathological features were retrospectively analyzed. Serum VEGF levels were correlated with clinicopathological features of the HCC patients. The patients' survival rates were analyzed with Kaplan-Meier survival curves and compared by the log-rank test. The prognostic significance of serum VEGF levels and factors related to survival rate were evaluated by univariate and multivariate analysis.Results: The median serum VEGF level in the HCC patients was 285 pg/ml (range 14−1,207 pg/ml), significantly higher than that of healthy controls (P=0.021). The serum VEGF levels were significantly correlated with platelet counts (r=0.396, P=0.002) but not other clinicopathological features. Patients with serum VEGF level >285 pg/ml had worse overall survival compared with those with serum VEGF level <285 pg/ml (P=0.002). By multivariate analysis, the serum VEGF level was a significant prognostic factor.Conclusion: High serum VEGF levels may predict poor prognosis of HCC after TACE. This study highlights the importance of tumor biomarker as a prognostic predictor in TACE therapy for HCC, which has an intrinsic problem of unavailability of histopathological prognostic features.

Transarterial chemoembolization combined with sorafenib for the treatment of hepatocellular carcinoma with hepatic vein tumor thrombus

“… 11 – 13 Moreover, an increase in vascular endothelial growth factor (VEGF) levels has been reported in patients treated with TACE and to predict poor prognosis. 12 , 14 The use of sorafenib can significantly counteract the tyrosine kinase receptors VEGFR-2/3 and platelet-derived growth factor receptor (PDGFR)-b, which decreases the post-TACE VEGF and PDGF upregulation and further enhances the efficacy of TACE. 15 , 16 Besides, sorafenib combined with cytotoxic drug shows a synergism that sorafenib inhibits the Ras/Raf/MEK/ERK pathway, which will prevent activation of the multidrug resistance pathway that leads to the failure of chemotherapy in treating HCC.…”

Expression and association of VEGF-Notch pathways in infantile hemangiomas

“…Numerous studies have shown that the VEGF family not only has a crucial impact on the tumorigenesis, development and invasion of many solid tumors such as gastrointestinal cancer, urinary cancer, nervous system tumors, but that VEGF signaling is also significant to the pathogenesis and prognosis of tumors in the blood and lymphatic system ( 8 ). VEGF-A is the ligand most involved in VEGFR-mediated angiogenesis and it can promote the differentiation of vascular progenitor cells into vascular endothelial cells ( 9 ).…”

Platelets and Hepatocellular Cancer: Bridging the Bench to the Clinics

“…Serum VEGF levels reflect both plasmatic and intra-platelet concentrations, and since plasma contains a substantially lower level of VEGF, platelets are the primary source of serum VEGF. Several studies were published focusing on the direct correlation between serum VEGF and HCC (Table 2) [36,56,57,58,59,60,61,62,63,64]. The ratio between serum VEGF and platelet count or platelet VEGF values alone were investigated in some studies on HCC, showing a direct correlation with tumor diameter [59], recurrence after local treatment [63], vascular invasion [56,64], and overall survival [56].…”

“…A recent meta-analysis based on 11 studies evaluating the correlation between serum VEGF level and survival in patients with HCC confirmed these data, showing that serum VEGF levels had an unfavorable impact on both disease-free (HR = 2.27, 95%CI = 1.55–2.98) and overall survival (HR = 1.88, 95%CI = 1.46–2.30) [61]. Overall, the increase in serum VEGF was a poor prognostic indicator in HCC patients undergoing several different treatments, such as radiotherapy, trans-arterial chemoembolization (TACE), resection, and liver transplantation [57,58,60,62,64].…”