Shimizu Yoshinori, Kondo Satoru, Shirai Akiko, Furukawa Mitsuru, Yoshizaki Tomokazu
Department of Otolaryngology, School of Medicine, Kanazawa University, Takaramachi 13-1, Ishikawa, Japan.
Auris Nasus Larynx. 2008 Sep;35(3):381-9. doi: 10.1016/j.anl.2007.12.002. Epub 2008 Feb 13.
Matrix 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).
In this study, we genotyped 69 tongue SCC patients. The expression of MMP-1 and IL-8 in tongue SCC patients was analyzed by immunohistochemistry.
We 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).
These 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.
基质金属蛋白酶-1(MMP-1)和白细胞介素-8(IL-8)在癌症发生和转移中起重要作用。MMP-1和IL-8启动子区域存在一个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基因型可增强转录活性,可能与恶性肿瘤风险增加有关。因此,我们评估了这些SNP在舌鳞状细胞癌(SCC)中的影响。
在本研究中,我们对69例舌SCC患者进行了基因分型。通过免疫组织化学分析舌SCC患者中MMP-1和IL-8的表达。
我们发现IL-8 A/A基因型与淋巴结复发存在显著差异(P=0.0068)。无病生存率分析表明,MMP-1 2G/2G和IL-8 A/A基因型同时存在与特别差的预后相关(P=0.0032),并且是一个独立的预后因素(P=0.001)。MMP-1的表达与MMP-1 2G/2G基因型的频率显著相关(P=0.049)。
这些结果表明,MMP-1和IL-8启动子区域的SNP通过其在舌SCC中的表达在肿瘤进展和复发中起重要作用。