血管內皮生長因子基因多型性及蛋白表現與翼狀贅片致病過程的相關性

研究目的：過去研究已證實血管內皮生長因子（VEGF）的基因表現與癌化過程相關。本研究假設血管內皮生長因子的基因多型性和蛋白表現與翼狀贅片的致病過程及治療的反應有關。研究方法及資料：本研究共採集60例翼狀贅片和121例正常球結膜組織，以即時定量聚合酶連鎖反應及免疫組織染色法分析基因型和VEGF蛋白的表現。並以初代培養之翼狀贅片細胞（PECs）細胞模式分析VEGF基因多型性對血管新生及藥物治療的影響。研究結果：60例翼狀贅片檢體中有48例（83.3％）的血管內皮生長因子蛋白表現檢測呈陽性，表現顯著高於較對照組（16.7％，P <0.0001）。在翼狀贅片組的 936 C>T變異比例顯著高於對照組，但-2578 C>A變異則在兩組間並無統計上的差異性。VEGF蛋白表現在 936的C/C組比936的C/T和T/T組顯著較高（P=0.001）。細胞模式的結果，顯示帶有C/C基因型的原發性翼狀贅片細胞（PECs）有較高的血管生成能力。在抗血管生成藥物bevacizumab處理後，帶C/C型的PECs細胞相較於C/T和TT基因型的細胞有更高的藥物敏感性。結論：根據上述結果建議VEGF 936 C>T基因多型性可用來作為治療翼狀贅片的患者的指標。

Objective：Vascular endothelial growth factor (VEGF) gene expression has been linked to cancer progression. Here we hypothesize that the polymorphism and protein expression of VEGF are correlated with the pathogenesis and therapy response of pterygium.Methods and Materials：A 60 pterygial and 121 normal conjunctival samples were collected to determine the genotypes and protein expression of VEGF. Primary pterygium cells (PECs) were used to confirm the effect of the VEGF polymorphism on the angiogenesis of pterygium. Results：48 (83.3%) pterygial specimens tested positive for VEGF protein expression, which was significantly higher than in the control groups (16.7%, p<0.0001). The frequency of the 936 C>T variant, but not the −2578C>A variant, was significantly higher in the pterygium group compared with the control group. VEGF protein expression was significantly higher in the 936 C/C group than in the 936 C/T and T/T groups (p=0.001). The results of our cell model showed that PECs with the C/C genotype had a higher angiogenesis ability and higher response to the antiangiogenesis drug bevacizumab than cells with the C/T and T/T genotypes. Conclusion：We suggest that VEGF could be used as a target for pterygium therapy in patients with the 936C>T genotype.