基质金属蛋白酶14基因在人喉鳞状细胞癌中表达差异的分析

Gene expression of matrix mettallo-proteinase 14 in laryngeal squamous cell carcinoma

目的 探讨基质金属蛋白酶14(matrix mettallo-proteinase 14,MMP14)即膜性基质金属蛋白酶(membrane type-1 matrix metalloproteinase,MT1-MMP)基因在喉癌中表达与喉癌临床病理生物学行为的关系。方法 从分子和蛋白质水平,研究MMP14在喉癌组织和其相邻的正常黏膜组织的表达差异,分析MMP14基因及其蛋白表达与喉癌临床病理生物学行为的关系。结果 33例配对喉癌标本中MMP14基因在26例喉癌组织中的表达明显高于其相应的正常黏膜组织,2例喉癌低表达,5例表达差异不明显。MMP14基因在不同分期的声门型喉癌中的表达差异无显著性(P>0.05),但在不同分化程度、有无淋巴结转移的声门型喉癌中,表达差异有显著性(P<0.05);在不同分期、不同分化程度及有无淋巴结转移的声门上型喉癌中,表达差异有显著性(P<0.05)。MMP14蛋白绝大多数位于癌巢细胞质内及癌巢间质内的成纤维细胞质内,在部分病例中有的正常黏膜细胞内不表达,有的表达;MMP14蛋白在绝大多数喉癌组织中的表达明显高于其相邻的正常黏膜组织。MMP14蛋白表达与MMP14基因表达基本是一致的。MMP14蛋白表达差异有显著性组患者的术后生存率与表达差异无显著性组的术后生存率无统计学差异(P>0.05)。结论 MMP14蛋白在喉癌的侵袭中可能只起一定的作用。

Objective To investigate the role of expression of matrix mettallo-proteinase 14 (MMP14) in laryngeal carcinomas and the relationship between MMP14 expression and the laryngeal biological behavior. Methods The gene expression differences of MMP14 between fresh laryngeal cancer tissues and their surrounding normal mucosa was analyzed by RT-PCR. The expression of MMP14 protein in paraffin-embedded tissues was determined immunohistochemically. All statistical analyses were performed by SPSS version 10.0. Results In the 33 cases of matched specimens, MMP14 gene expression was much higher in tumor tissues than that in surrounding ing normal tissues in 26 cases and lower in 2 cases, whereas in other 5 cases, no significant difference was observed between the cancer tissue and the surrounding normal tissue. MMP14 gene expression was not different in different stages in laryngeal glottic cancers, but correlated to the differentiation and lymph node metastasis (P < 0. 05 ) . There was correlation between MMP14 gene expression and the stage, differentiation and lymph node metastasis in the laryngeal supraglottic cancers ( P < 0. 05 ). MMP14 protein was localized predominantly in the carcinoma cell cytoplasm and in the stromal fibroblast cytoplasm, and weakly or not expressed in surrounding normal tissue. MMP14 protein expression was much higher in tumor tissue than that in surrounding normal tissue in most of the cases. In general, MMP14 protein expression was the same as MMP14 gene expression and related to the stage, differentiation and lymph node metastasis in the laryngeal cancers. There was no survival difference at 3, 5 and 7-year between the group with higher MMP14 protein expression in tumor tissues than surrounding normal tissues and the group with no difference of MMP14 protein expression ( Log Rank, P = 0. 5535 ) . Conclusions The protein MMP14 may play role in laryngeal cancer invasion in a certain extent, but important role in lymph node metastasis of laryngeal cancer. The over-expression of MMP14 protein may be a marker for lymph node metastasis of laryngeal cancer.