Ben Néjima Dalel, Ben Zarkouna Yosr, Pujol Pascal, Gammoudi Amor, Boussen Hamouda, Manai Mohamed
*Unité de biochimie et de biologie moléculaire, Faculté des Sciences de Tunis †Service d'oncologie médicale Hôpital Abderrahmen Mami, Ariana §Service d'anatomopathologie, Institut Salah Azaiez, Tunis, Tunisie ‡Unité d'oncogénétique, Hôpital Arnaud de Villeneuve, Montpellier, France.
Appl Immunohistochem Mol Morphol. 2017 Jan;25(1):64-70. doi: 10.1097/PAI.0000000000000263.
Matrix metalloproteinase-2 (gelatinase A) is a well-known mediator of cancer metastasis, but it is also thought to be involved in several aspects of cancer development, including cell growth and inflammation. In the present study, we investigate whether MMP-2 SNP, MMP-2 mRNAs, and MMP-2 protein are associated with the susceptibility to colorectal cancer in the Tunisian population. The TaqMan allele discrimination assay and DNA sequencing techniques were used for genotyping; MMP-2 expression of each genotype was analyzed by semiquantitative RT-PCR, and MMP-2 protein expression was analyzed by immunohistochemistry staining. Our result showed that the levels of MMP-2 mRNA expression in patients containing the CC genotype were much higher compared with cells with the CT genotype. The frequency of the MMP-2 CC genotype was significantly higher in colorectal cancer patients when compared with controls (OR=1.94; 95% CI, 1.117-3.680). A higher intensity of staining of MMP-2 was observed in regions of invasion of the muscularis mucosa compared with superficial portions of the tumor. In addition, we found a significant progressive increase in total MMP-2 plasma levels with progression from adenomatous polyps through advancing Dukes stages (P=0.0001). Our data suggest that MMP-2 may be associated with colorectal cancer development and invasion in the Tunisian population; moreover, SNP and levels of MMP-2 could be a predictive value for colorectal cancer prevention and invasiveness.
基质金属蛋白酶-2（明胶酶A）是一种众所周知的癌症转移介质，但人们也认为它参与癌症发展的多个方面，包括细胞生长和炎症。在本研究中，我们调查了基质金属蛋白酶-2单核苷酸多态性（MMP-2 SNP）、MMP-2信使核糖核酸（MMP-2 mRNAs）和MMP-2蛋白是否与突尼斯人群患结直肠癌的易感性相关。采用TaqMan等位基因鉴别分析和DNA测序技术进行基因分型；通过半定量逆转录聚合酶链反应（RT-PCR）分析每种基因型的MMP-2表达，并通过免疫组织化学染色分析MMP-2蛋白表达。我们的结果显示，与携带CT基因型的细胞相比，含有CC基因型的患者中MMP-2 mRNA表达水平要高得多。与对照组相比，结直肠癌患者中MMP-2 CC基因型的频率显著更高（比值比=1.94；95%置信区间，1.117 - 3.680）。与肿瘤浅表部分相比，在黏膜肌层浸润区域观察到MMP-2染色强度更高。此外，我们发现随着从腺瘤性息肉到进展期杜克分期的进展，血浆中MMP-2的总水平显著逐渐升高（P = 0.0001）。我们的数据表明，MMP-2可能与突尼斯人群的结直肠癌发展和侵袭相关；此外，MMP-2的单核苷酸多态性和水平可能对结直肠癌的预防和侵袭性具有预测价值。
