Correlations of the expression of vascular endothelial growth factor B and its isoforms in hepatocellular carcinoma with clinico-pathological parameters.

BACKGROUND: The vascular endothelial growth factor (VEGF) is involved in the growth of cancer cells through angiogenesis. At present the role of VEGF-B has not been clarified completely. We investigated correlations of the expression of VEGF-B and its isoforms, VEGF-B167 and VEGF-B186, by alternative splicing in hepatocellular carcinoma (HCC) with the pathological findings and prognosis. METHODS: Forty-eight patients with HCC were investigated. We examined the mRNA expression of total VEGF-B, VEGF-B167 and VEGF-B186 in primary HCC and non-cancerous tissues using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) analysis. RESULTS: In 16 (33.3%) of 48 HCCs, the expression of total VEGF-B increased compared with the corresponding non-cancerous liver tissues. Regarding the isoforms, the expression of VEGF-B167 and VEGF-B186 was increased in 17 (35.4%) of 48 and 33 (68.75%) of 48 HCCs, respectively. Cases with high expression level of total VEGF-B in HCC significantly correlated with the advanced pathological stage (P < 0.018), tumor multiplicity (P < 0.033), vascular invasion (P < 0.045) and lack of capsule formation (P < 0.027). The result in VEGF-B167 was similar to total VEGF-B. CONCLUSIONS: Our results indicated that the expression of VEGF-B is correlated with tumor growth and invasiveness in HCC. VEGF-B167 seemed to be the clinically dominant isoform.