缺氧诱导因子1α的多态性对食管鳞癌血管生成的影响

The common single nucleotide polymorphism of hypoxia-inducible factor 1α gene exerts some influence on angiogenesis of human esophageal squamous cell carcinoma

目的:血管生成是恶性肿瘤形成与发展中的重要事件,缺氧诱导因子1及其调节的VEGF的表达对食管鳞癌的血管生成和临床病理学特征具有重要的意义。该研究旨在研究缺氧诱导因子1α的常见多态性C1772T对食管鳞癌血管生成的影响,并初步探讨其机制。方法:用PCR-RFLP法研究95例食管鳞癌、104例正常对照的缺氧诱导因子1α的常见多态性C1772T的基因型(突变者经直接测序确认);免疫组化法测定不同基因型肿瘤组织中缺氧诱导因子1α(HIF-1α)、内皮源性生长因子VEGF、微血管密度MVD;比较不同基因型肿瘤的HIF鄄1α、VEGF、CD34(用以标记MVD)的表达差异。结果:在病例和对照中,只发现C/C和C/T两种基因型,食管鳞癌组C1772T的突变率为11.58%(11/95),正常对照组为10.58%(11/104),两组相比没有统计学差异;C/T组和C/C组肿瘤组织相比,HIF鄄1α表达无差异,VEGF的表达上调,MVD明显增加。结论:HIF鄄1α基因单核苷酸多态性C1772T与食管鳞癌的VEGF高表达和增强的血管生成有关。

Objectives: To investigate the impact of single nucleotide polymorphism(C1772T) of hypoxia-inducible factor 1α gene on angiogenesis of human esophageal squamous cell carcinoma. Methods: Genotype of C1772T of 95 cases of ESCC patients and 104 healthy controls were studied by PCR-RFLP. Mutation was confirmed by direct DNA sequencing. The expression of HIF-1α,CD34,VEGF was determined immunohistochemmically in paraffin-embedded specimens of ESCC patients. Results: The genotype frequency observed in the patients and controls was 11.58% versus 10.58% respectively (P > 0.05) for genotype C/T. Genotype T/T was not found in our study. VEGF and CD34 were more highly expressed in specimens of patients with rare allele C/T. But expression levels of HIF-1α between C/T and C/C groups shew no significant difference. Conclusion: Although there is no significant difference of genotype distribution between ESCC patients and healthy controls, C1772T is associated with higher expression of VEGF and enhanced angiogenesis of this malignancy.