Cancer Molecular Pathology, Griffith Health Institute, Griffith University, Gold Coast, Queensland 4222, Australia.
Eur J Surg Oncol. 2011 Jan;37(1):93-9. doi: 10.1016/j.ejso.2010.10.010. Epub 2010 Nov 18.
Polymorphisms of the VEGF gene are known to affect the biological behaviour of cancers but have seldom been studied in thyroid cancer. The aim of the current study is to evaluate the prevalence and relevance of VEGF-A polymorphisms and mRNA expression in papillary thyroid carcinoma (PTC).
Genomic DNA and total RNA were isolated from paraffin-embedded tissue from 91 PTC (51 conventional PTC and 40 follicular variant) and 78 control thyroid tissues. Three DNA polymorphisms (+936C > T, +405C > G and -141A > C) in the 3' and 5' untranslated region (3'-UTR, 5'-UTR) of VEGF-A were studied using PCR and RFLP. Also, the mRNA expression of VEGF-A in these tissues was studied by real-time PCR.
Distribution of polymorphisms in the 5'-UTR (VEGF-VEGF -141A > C and +405C > G) and 3'-UTR (VEGF +936C > T) were all significantly different in PTC and benign thyroid tissue (p = 0.0001, 0.001 and 0.028 respectively). The VEGF -141 C allele was more common in PTC with lymph node metastases (p = 0.026). VEGF + 405 Galleles andVEGF +936 CC genotype were more common in PTC of advanced pathological staging (p = 0.018 and 0.017 respectively). Also, increased expression of VEGF-A mRNA was noted in PTC compared to control (p = 0.009). Within the group of patients with conventional PTC, those with lymph nodal metastases had a higher level of VEGF-A mRNA expression than other patients (p = 0.0003).
These findings suggest that VEGF polymorphisms and mRNA expression may predict the aggressiveness behaviour of thyroid cancer.
血管内皮生长因子（VEGF）基因的多态性已知会影响癌症的生物学行为，但在甲状腺癌中很少有研究。本研究旨在评估 VEGF-A 多态性及其 mRNA 表达在甲状腺乳头状癌（PTC）中的发生率和相关性。
从 91 例 PTC（51 例传统 PTC 和 40 例滤泡状癌）和 78 例对照甲状腺组织的石蜡包埋组织中分离基因组 DNA 和总 RNA。采用 PCR 和 RFLP 方法研究 VEGF-A 3'和 5'非翻译区（UTR）中的三个 DNA 多态性（+936C>T、+405C>G 和-141A>C）。还通过实时 PCR 研究了这些组织中 VEGF-A 的 mRNA 表达。
PTC 和良性甲状腺组织中 5'-UTR（VEGF-VEGF-141A>C 和 +405C>G）和 3'-UTR（VEGF+936C>T）的多态性分布均有显著差异（p=0.0001、0.001 和 0.028）。VEGF-141 C 等位基因在有淋巴结转移的 PTC 中更为常见（p=0.026）。VEGF+405G 等位基因和 VEGF+936CC 基因型在晚期病理分期的 PTC 中更为常见（p=0.018 和 0.017）。此外，与对照组相比，PTC 中 VEGF-A mRNA 的表达增加（p=0.009）。在传统 PTC 患者中，有淋巴结转移的患者 VEGF-A mRNA 表达水平高于其他患者（p=0.0003）。
这些发现表明 VEGF 多态性和 mRNA 表达可能预测甲状腺癌的侵袭性行为。
