Hepatocellular carcinoma (HCC) remains a major global health challenge, with limited effective systemic therapies. The development of targeted agents inhibiting tumor angiogenesis has emerged as a promising strategy, particularly those directed against vascular endothelial growth factor (VEGF), a key driver of neovascularization in HCC. Drugs such as sorafenib and lenvatinib—both multi-kinase inhibitors targeting VEGF receptors—have become standard treatments for advanced HCC. However, patient responses vary widely, and biomarkers capable of predicting therapeutic efficacy are urgently needed.
Several clinical trials have investigated the relationship between baseline VEGF expression levels in tumor tissue and response to anti-angiogenic therapy. While some studies reported that high VEGF expression correlates with better outcomes, others found no association or even worse survival in VEGF-positive patients. This inconsistency may stem from differences in study design, treatment regimens, assessment methods, and patient selection. To resolve this controversy, we conducted a meta-analysis of available clinical trials evaluating the impact of VEGF expression on treatment response and survival outcomes in patients with advanced HCC receiving anti-angiogenic therapy.
We included nine randomized controlled trials and cohort studies involving 1,042 patients treated with sorafenib, lenvatinib, or other VEGF-targeted agents. All studies provided data on tumor VEGF expression assessed via immunohistochemistry (IHC) or RT-PCR, along with objective response rates (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Data were extracted independently by two reviewers, and hazard ratios (HRs) and odds ratios (ORs) were calculated using published survival curves or directly reported values.
Our analysis revealed that patients with high VEGF expression had significantly higher objective response rates (OR = 2.2-Cyanothiazole Autophagy 35, 95% CI: 1.67–3.30; P < 0.001) and improved disease control rates (OR = 2.D-Panthenol custom synthesis 18, 95% CI: 1.54–3.08; P < 0.001) compared to those with low expression. These findings suggest that tumors with elevated VEGF levels may be more dependent on angiogenic signaling and thus more susceptible to VEGF inhibition.PMID:35076956
Moreover, high VEGF expression was associated with longer progression-free survival (HR = 0.69, 95% CI: 0.56–0.85; P = 0.001) and improved overall survival (HR = 0.76, 95% CI: 0.62–0.94; P = 0.012). Subgroup analyses showed consistent results across different drugs, including sorafenib and lenvatinib, indicating that the predictive value of VEGF is not drug-specific but rather reflects underlying tumor biology.
Sensitivity analyses excluding individual studies did not alter the direction or significance of the results, confirming robustness. No significant publication bias was detected using Begg’s and Egger’s tests (P > 0.05), suggesting that the findings reflect the true effect size rather than selective reporting.
Notably, the benefit of VEGF positivity was most pronounced in patients with moderate to high expression levels, while those with very low or absent expression derived minimal benefit. This supports the concept of “angiogenic dependency” where tumors reliant on VEGF pathways respond better to targeted inhibition.
In conclusion, this meta-analysis provides strong evidence that high pre-treatment VEGF expression in hepatocellular carcinoma is a favorable predictor of response to anti-angiogenic therapy, including improved objective response, disease control, and prolonged survival. These findings underscore the potential of VEGF as a companion diagnostic to guide personalized treatment decisions. Future prospective trials should validate these results in larger cohorts and explore whether combining VEGF status with other molecular markers can further refine patient selection for anti-angiogenic therapies.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com