Korean J Hepatol.  2008 Jun;14(2):185-196. 10.3350/kjhep.2008.14.2.185.

Expression of vascular endothelial growth factor (VEGF) family members and prognosis after hepatic resection in HBV-related hepatocellular carcinoma

• Moon JI
• Kim JM
• Jung GO
• Chun JM
• Choi GS
• Park JB
• Kwon CH
• Kim SJ
• Jo JW

• KMID: 760783
• DOI: http://doi.org/10.3350/kjhep.2008.14.2.185

Abstract

BACKGROUND/AIMS: Human hepatocellular carcinoma (HCC) is a hypervascular tumor, and vascular endothelial growth factor (VEGF) plays a key role in the regulation of tumor-associated angiogenesis. In this study, we analyzed the significance of the expression of VEGF family members on the prognosis and clinicopathologic progress of HCC. METHODS: Surgically resected specimens of HCC and noncancerous liver tissue were obtained from 323 patients with HCC, and VEGF mRNA was examined by quantitative reverse transcriptase-polymerase chain reactions (RT-PCRs). Patients who were seropositive for hepatitis B surface antigen were selected for the analysis (n=208). The VEGF(tumor)/GAPDH (glyceraldehyde-3-phosphate dehydrogenase)(tumor)/VEGF(nontumor)/GAPDH(nontumor) ratio was calculated using a quantitative RT-PCR assay, and the relationships between the expressions of VEGF family members and clinicopathologic parameters were analyzed to evaluate their significance in the prognosis of HCC. RESULTS: The disease-free survival was significantly worse in the high-VEGF-A group than in the low-VEGF-A group (P=0.035), whereas VEGF-A expression was not significantly related to overall survival (P=0.172). The factors significantly related to poor prognosis in univariate analysis were tumor size, portal vein invasion, microvascular thrombi, intrahepatic metastasis, tumor capsule invasion, liver capsule invasion, preoperative serum albumin level, and VEGF-A ratio. Multivariate analysis showed that a poor prognosis in HCC patients was significantly related to portal vein invasion (hazard ratio=3.381, P<0.001), intrahepatic metastasis (hazard ratio=2.379, P<0.001), tumor size (hazard ratio=1.834, P=0.003), and preoperative serum albumin level (hazard ratio=2.050, P=0.006). CONCLUSIONS: Our study showed that the expression of VEGF-A is positively correlated with the recurrence rate of HCC after curative resection. Therefore, a high expression of VEGF-A might be predictive of HCC recurrence after curative resection.

Keyword

Carcinoma, hepatocellular; Vascular endothelial growth factors; Recurrence

MeSH Terms

Adult
Aged
Base Sequence
Carcinoma, Hepatocellular/*diagnosis/*surgery/virology
Female
Hepatitis B/complications
Hepatitis B Surface Antigens/blood
Humans
Liver Neoplasms/*diagnosis/*surgery/virology
Male
Middle Aged
Molecular Sequence Data
Multivariate Analysis
Neoplasm Invasiveness
Neoplasm Staging
Predictive Value of Tests
Prognosis
RNA, Messenger/analysis
Reverse Transcriptase Polymerase Chain Reaction
Survival Analysis
Vascular Endothelial Growth Factors/genetics/*metabolism