Prognostic significance of preoperative circulating vascular endothelial growth factor messenger RNA expression in resectable hepatocellular carcinoma: A prospective study

Aim: To investigate the prognostic value of vascular endothelial growth factor messenger RNA (VEGF mRNA) in the peripheral blood (PB) of patients with hepatocellular carcinoma (HCC) undergoing curative resection. Methods: Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, VEGF mRNA in the PB was determined prospectively in 50 controls and in 50 consecutive patients undergoing curative resection for HCC. Results: Among the isoforms of VEGF mRNA, VEGF₁₆₅ and VEGF₁₂₁ were expressed. By multivariate analysis, a higher level of VEGF₁₆₅ in preoperative PB correlated with a risk of HCC recurrence with borderline significance (P=0.050) and significantly with recurrence-related mortality (P=0.048); while VEGF₁₂₁ did not. Other significant predictors of HCC recurrence included cellular dedifferentiation (P=0.033), an absent or incomplete capsule (P=0.020), vascular permeation (P=0.018), and daughter nodules (P=0.006). The other significant parameter of recurrence related mortality was cellular dedifferentiation (P=0.053). The level of circulating VEGF mRNA, however, did not significantly correlate with tumor size, cellular differentiation, capsule, daughter nodules, vascular permeation, necrosis and hemorrhage of tumors. Conclusion: The preoperative level of circulating VEGF mRNA, especially isoform VEGF₁₆₅, plays a significant role in the prediction of postoperative recurrence of HCC.