Prognostic role of vascular endothelial growth factor in hepatocellular carcinoma: systematic review and meta-analysis

Abstract

Hepatocellular carcinoma (HCC) is a highly vascular tumour that expresses vascular endothelial growth factor (VEGF). Various studies have evaluated the prognostic value of VEGF levels in HCC. Its overall test performance remains unclear, however. The aim was to perform a systematic review and meta-analysis of prognostic cohort studies evaluating the use of VEGF as a predictor of survival in patients with treated HCC. Eligible studies were identified through multiple search strategies. Studies were assessed for quality using the Newcastle–Ottawa Tool. Data were collected comparing disease-free and overall survival in patients with high VEGF levels as compared to those with low levels. Studies were pooled and summary hazard ratios were calculated. A total of 16 studies were included for meta-analysis (8 for tissue and 8 for serum). Methodological analysis indicated a trend for higher study quality with serum studies as compared to tissue-based investigations. Four distinct groups were pooled for analysis: tissue overall survival ( n =251), tissue disease-free survival ( n =413), serum overall survival ( n =579), and serum disease-free survival ( n =439). High tissue VEGF levels predicted poor overall (HR=2.15, 95% CI: 1.26–3.68) and disease-free (HR=1.69, 95% CI: 1.23–2.33) survival. Similarly, high serum VEGF levels predicted poor overall (HR=2.35, 95% CI: 1.80–3.07) and disease-free (HR=2.36, 95% CI 1.76–3.16) survival. A high degree of inter-study consistency was present in three of four groups analysed. Tissue and serum VEGF levels appear to have significant predictive ability for estimating overall survival in HCC and may be useful for defining prognosis in HCC.

CD151 modulates expression of matrix metalloproteinase 9 and promotes neoangiogenesis and progression of hepatocellular carcinoma

“…9A. Similarly to a previous study, 34 high tissue VEGF levels predicted poor OS and higher cumulative recurrence rates in HCC patients (unpublished data), whereas correlation analysis showed that there was a slight association between the expression of CD151 and VEGF (r CD151 vs. VEGF ¼ 0.115, P ¼ 0.037). Therefore, we infer that overexpression of CD151 probably up-regulated the expression of MMP9 and subsequently facilitated the formation of new vessels in HCCs.…”

Effects of melatonin on HIF-1α and VEGF expression and on the invasive properties of hepatocarcinoma cells

“…The decrease in the expression of HIF-1α and VEGF proteins in HepG2 cells following melatonin treatment in the present study is of particular interest as increased expression of HIF-1α (39) and VEGF (7,39) correlates with unfavorable prognostic features, including large tumor size and reduced survival in patients with hepatocellular carcinoma.…”

“…This factor is involved in angiogenesis in multiple tumor types, promoting growth, spread and tumor metastasis (5). Previous studies have correlated increased VEGF expression with poor prognosis in HCC (6,7).…”

Current management of hepatocellular carcinoma: An Eastern perspective

“…Therefore, control of VEGF signaling and of other tumor growth factors is necessary to prevent the progression and recurrence of HCC in patients receiving TACE [145] . A randomized controlled trial was conducted in Japan and Korea to assess the effects of TACE plus sorafenib [146] .…”