A single nucleotide polymorphism in the matrix metalloproteinase-1 and interleukin-8 gene promoter predicts poor prognosis in tongue cancer.
A single nucleotide polymorphism in the matrix metalloproteinase-1 and interleukin-8 gene promoter predicts poor prognosis in tongue cancer.
复制标题
DOI：
10.1016/j.anl.2007.12.002
复制
发表时间：
2008-09
期刊：
影响因子：
--
通讯作者：
Y. Shimizu;S. Kondo;Akiko Shirai;M. Furukawa;T. Yoshizaki
中科院分区：
文献类型：
--
作者：
Y. Shimizu;S. Kondo;Akiko Shirai;M. Furukawa;T. Yoshizaki
基质金属蛋白酶-1（MMP-1）和白细胞介素-8（IL-8）在肿瘤的发生和转移中起重要作用。在MMP-1和IL-8的启动子区域存在调节基因表达的单核苷酸多态性（SNP）。MMP-1 −1607 2G/2G和IL-8 −251 A/A基因型增强转录活性，可能与恶性肿瘤风险增加有关。因此，我们评估了这些SNPs在舌鳞状细胞癌（SCC）的影响。METHODS在这项研究中，我们对69例舌鳞状细胞癌患者进行了基因分型。免疫组化法检测MMP-1和IL-8在舌鳞癌组织中的表达，结果发现IL-8 A/A基因型与淋巴结复发有显著性差异（P=0.0068）。无病生存率分析显示，MMP-1 2G/2G和IL-8 A/A基因型的存在与特别差的预后相关（P=0.0032），并且是独立的预后因素（P=0.001）。MMP-1的表达与MMP-1 2G/2G基因型频率显著相关（P=0.049）。结论MMP-1和IL-8基因启动子区SNP在舌鳞癌中的表达与肿瘤的进展和复发密切相关。
OBJECTIVEMatrix metalloproteinase-1 (MMP-1) and interleukin-8 (IL-8) play an important role in cancer development and metastasis. There is a single nucleotide polymorphism (SNP) located in the promoter region of MMP-1 and IL-8 that regulates gene expression. MMP-1 −1607 2G/2G and IL-8 −251 A/A genotypes enhance transcriptional activity and may be associated with increased risk in malignant tumors. We therefore evaluated the impact of these SNPs in tongue squamous cell carcinoma (SCC).METHODSIn this study, we genotyped 69 tongue SCC patients. The expression of MMP-1 and IL-8 in tongue SCC patients was analyzed by immunohistochemistry.RESULTSWe found a significant difference in IL-8 A/A genotypes with nodal recurrence (P=0.0068). An analysis of disease-free survival rates showed that the presence of both MMP-1 2G/2G and IL-8 A/A genotypes was associated with a particularly poor prognosis (P=0.0032) and was an independent prognostic factor (P=0.001). The expression of MMP-1 was significantly correlated with the frequency of MMP-1 2G/2G genotypes (P=0.049).CONCLUSIONThese results suggest that SNP in the promoter region of MMP-1 and IL-8 plays an important role in tumor progression and recurrence through its expression in tongue SCC.