Expression of vascular endothelial growth factor (VEGF) family members and prognosis after hepatic resection in HBV-related hepatocellular carcinoma |
Ju Ik Moon, M.D., Jong Man Kim, M.D., Gum Oh Jung, M.D.,
Jae Min Chun, M.D., Gyu-Seong Choi, M.D., Jae Berm Park, M.D.,
Choon Hyuck David Kwon, M.D., Sung Joo Kim, M.D., Jae Won Jo, M.D., |
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea |
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ABSTRACT |
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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 VEGFtumor/GAPDH (glyceraldehyde-3-phosphate dehydrogenase)
tumor/VEGFnontumor/GAPDHnontumor 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. (Korean J Hepatol 2008;14:185-196) |
KeyWords:
Carcinoma, hepatocellular; Vascular endothelial growth factors; Recurrence |
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