Evaluation of significant gene expression changes in congenital and acquired cholesteatoma

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ORIGINAL ARTICLE

Evaluation of significant gene expression changes in congenital and acquired cholesteatoma İsa Kaya1   · Çığır Biray Avcı2   · Fetih Furkan Şahin1   · Neslihan Pınar Özateş2   · Baha Sezgin1   · Cansu Çalışkan Kurt2   · Cem Bilgen1   · Tayfun Kirazlı1  Received: 19 February 2020 / Accepted: 26 July 2020 © Springer Nature B.V. 2020

Abstract 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 > 0.05 > 0.05 > 0.05 > 0.05

Significantly higher in acquired cholesteatoma are highlighted in bold These mean levels are indicated proportionally to the mean healthy tissue levels − means decrease

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Table 3  The comparison between pediatric and adult acquired cholesteatoma Gene

Pediatric acquired cholesteaoma

Adult acquired cholesteatoma

p Value

MMP-1 MMP-2 MMP-3 MMP-7 MMP-8 MMP-9 MMP-10 MMP-11 MMP-12 MMP-13 MMP-14 MMP-15 MMP-16 TIMP-1 TIMP-2 EGFR

1.47 2.48 1.03 1.62 0.39 58.59 2.53 68.24 1.57 511.35 41.38 9.37 87.14 − 1.97 − 6.45 20.85

1.83 2.28 0.68 1.88 0.33 19.80 2.19 58.17 1.22 238.95 4.79 8.82 66.25 − 1.67 − 4.21 23.94

> 0.05 > 0.05 > 0.05 > 0.05 > 0.05  0.05 > 0.05 > 0.05  0.05 > 0.05 > 0.05 > 0.05

Significantly higher in pediatric acquired cholesteatoma are highlighted in bold These mean levels are indicated proportionally to the mean healthy tissue levels − means decrease

advantages such as high precision and sensitivity and minimized risk of cross contamination [14]. In this section, first, we discussed the association between MMP, TIMP and EGFR expression levels and development of cholesteatoma and then the association between these genes and disease severity based on the expression changes. Previous studies showed that MMP genes are directly associated with physiologic and pathologic osteolytic activities [15]. Additionally, the basal cell layers of the cholesteatoma epithelium and stroma of the cholesteatoma express the MMP enzymes [6, 7]. MMPs are known as proteolytic enzymes that digest the type 4 collagen of the basal membrane. It is also reported that the overexpression of c-MYC, a well-known protooncogene, has been detected in ch