Department of Otorhinolaryngology, Ege University School of Medicine, Izmir, Turkey.
Department of Medical Biology, Ege University School of Medicine, Izmir, Turkey.
Mol Biol Rep. 2020 Aug;47(8):6127-6133. doi: 10.1007/s11033-020-05689-9. Epub 2020 Aug 1.
Etiopathogenesis of acquired and congenital cholesteatoma is still unclear. The clinical behavior of adult acquired, pediatric acquired and congenital cholesteatomas show differences. The scope of the this study was to detect the matrix metalloproteinase (MMP), tissue inhibitors of metalloproteinase (TIMP) and epidermal growth factor receptor (EGFR) gene expression changes in cholesteatoma perimatrix and to compare these changes among congenital cholesteatoma, adult acquired cholesteatoma and pediatric acquired cholesteatoma. A total of 16 genes including MMPs, TIMPs and EGFR were analyzed in the samples of 32 cholesteatoma tissues. Real-time PCR was used for detection of the gene expression levels. Data analyses were achieved by ΔΔCT method (Light Cycler 480 Quantification Software) and Statistical Package for Social Sciences (SPSS) version 22.0. The expression levels of MMP-2, -9, -10, -11, -13, -14, -15, -16 and EGFR genes were significantly higher in acquired cholesteatoma than healthy tissue (p < 0.05). There was a statistically significant decrease (3.34 times more) in the mean TIMP-2 gene expression level in acquired cholesteatoma compared to healthy tissue (p < 0.05). There was a significant increase in the mean expression level of MMP-7 gene and a decrease in the mean expression level of TIMP-1 gene (3.12 times more) in congenital cholesteatoma compared to healthy tissue (p < 0.05). This study indicates that increased expression levels of some particular MMP genes and EGFR gene and decreased expression levels of TIMP genes may play an important role in the development of cholesteatoma. Further, MMP-9, MMP-13 and MMP-14 genes may have a remarkable role in the development of more aggressive cholesteatoma forms. The authors concluded that overexpression of MMP-9, MMP-13 and MMP-14 may cause stronger inflammation associated with cholesteatoma.
获得性和先天性胆脂瘤的病因仍然不清楚。成人获得性、儿童获得性和先天性胆脂瘤的临床行为表现出差异。本研究的范围是检测胆脂瘤基质中的基质金属蛋白酶（MMP）、金属蛋白酶组织抑制剂（TIMP）和表皮生长因子受体（EGFR）基因表达的变化，并比较先天性胆脂瘤、成人获得性胆脂瘤和儿童获得性胆脂瘤之间的这些变化。在 32 例胆脂瘤组织样本中分析了包括 MMPs、TIMPs 和 EGFR 在内的 16 个基因。采用实时 PCR 检测基因表达水平。采用 ΔΔCT 法（Light Cycler 480 Quantification Software）和统计软件包（SPSS）版本 22.0 进行数据分析。MMP-2、-9、-10、-11、-13、-14、-15、-16 和 EGFR 基因的表达水平在获得性胆脂瘤中明显高于健康组织（p<0.05）。与健康组织相比，获得性胆脂瘤中 TIMP-2 基因的平均表达水平显著降低（降低 3.34 倍）（p<0.05）。与健康组织相比，先天性胆脂瘤中 MMP-7 基因的表达水平显著升高，TIMP-1 基因的表达水平显著降低（降低 3.12 倍）（p<0.05）。本研究表明，某些特定的 MMP 基因和 EGFR 基因的表达水平升高以及 TIMP 基因的表达水平降低可能在胆脂瘤的发生发展中起重要作用。此外，MMP-9、MMP-13 和 MMP-14 基因可能在更具侵袭性的胆脂瘤形式的发展中起重要作用。作者得出结论，MMP-9、MMP-13 和 MMP-14 的过度表达可能导致与胆脂瘤相关的更强炎症。
