血管內皮生長因子C (VEGF-C)之基因多型性在肝細胞癌的易感受性與其病理發展的角色

血管內皮生長因子-C (vascular endothelial growth factor-C；VEGF-C)，是一個會在腫瘤組織中高度表現的血管/淋巴管生長因子，其在許多惡性腫瘤中，包括肝細胞癌(Hepatocellular carcinoma；HCC)的發展上扮演著重要的角色。本篇研究目的是探討VEGF-C的基因多型性與肝細胞癌的易感受性及其臨床病理發展上是否相關。我們利用即時定量聚合酶連鎖反應(real-time PCR)分析135位肝細胞癌患者和520位非癌症對照組其VEGF-C基因多型性表現的情形。結果我們發現具有VEGF-C rs1485766 A/A基因型的人與野生型同型合子的人相比，其罹患肝細胞癌的風險較高，並具顯著差異(P = 0.021)；而肝細胞癌患者表現VEGF-C rs7664413 CT/TT基因型者有較高的機率發展成晚期肝細胞癌，而具有VEGF-C rs3775194 GC/CC基因型者則有較低的機率發展成肝硬化。此外，我們也發現來自五種VEGF-C的單核苷酸基因多型性(Single-Nucleotide Polymorphisms；SNPs)中單倍型的結合(GGACA、GACTG、CGATG和GGCTG)也與罹患肝細胞癌的風險有關。統合以上的研究結果發現，VEGF-C rs1485766的單核苷酸基因多型性或來自五種VEGF-C多型性之單倍型結合，可能有助於預測肝細胞癌的感受性；而VEGF-C rs7664413的基因多型性可能是肝細胞癌是否會進展到晚期的一個預測因子。

關鍵字

血管內皮生長因子-C ；肝細胞癌；基因多型性

並列摘要

Vascular endothelial growth factor (VEGF)-C, an angiogenic/ lymphangiogenic factor with high expression levels in tumor tissues, plays important roles in the development of several malignancies including hepatocellular carcinoma (HCC). The purpose of this study was to examine whether VEGF-C gene polymorphisms are associated with susceptibility to HCC and its clinicopathological development. Genetic polymorphisms of VEGF-C of 135 patients with HCC and 520 non-cancer controls were analyzed by a real-time polymerase chain reaction (PCR). We found that a significantly (p=0.021) higher risk for HCC was shown in individuals with the VEGF-C rs1485766 A/A genotype compared to those with wild-type homozygotes; a high frequency of an advanced stage and a low frequency of being positive for cirrhosis were respectively shown in HCC patients with the VEGF-C rs7664413 CT/TT and rs3775194 GC/CC genotypes. Moreover, we found that the GGACA, GACTG, CGATG, and GGCTG haplotypes of five VEGF-C single-nucleotide polymorphisms (SNPs) combined were also related to the risk of HCC. In conclusion, our results suggest that the VEGF-C rs1485766 SNP and either of five haplotypes combined might contribute to a prediction of susceptibility to HCC. More importantly, the genetic polymorphism of VEGF-C rs7664413 might be a predictive factor for advanced-stage HCC.

並列關鍵字

vascular endothelial growth factor C ； hepatocellular carcinoma ； singlenucleotide polymorphism

參考文獻

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血管內皮生長因子C (VEGF-C)之基因多型性在肝細胞癌的易感受性與其病理發展的角色

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