HB-EGF expression as a potential biomarker of acquired middle ear cholesteatoma

Abstract

Conclusions: The heparin-binding epidermal growth factor-like growth factor (HB-EGF) plays an essential role in the development and invasiveness of cholesteatoma. This study may help to realize the molecular mechanisms underlying the pathogenesis of cholesteatoma and make HB-EGF a promising target for drug intervention of cholesteatoma.

Objective: To detect HB-EGF expression in human surgical specimens of acquired middle ear cholesteatoma and analyze its functional role as a regulator of epithelial keratinocytes hyperproliferation.

Methods: A total of 34 patients who underwent surgical treatment for middle ear cholesteatoma were recruited in the study. The mRNA and protein expression of HB-EGF in middle ear cholesteatoma tissues and normal postauricular skin tissues was investigated by real-time quantitative reverse-transcription-polymerase chain reaction (RT-qPCR), immunohistochemical staining, and western blot. The correlation between bone resorption degree and HB-EGF expression was also analyzed.

Results: On average, compared with normal postauricular skin, expression of HB-EGF mRNA in the cholesteatoma epithelium was significantly elevated 2.41-fold by RT-qPCR, and HB-EGF protein significantly upregulated 2.32-fold by western blot. Positive HB-EGF immunostaining observed in the basal and suprabasal layers of cholesteatoma epithelium was significantly stronger than in normal postauricular skin. Meanwhile, an obviously positive correlation between HB-EGF protein expression and bone resorption degree was discovered.

Chinese abstract

结论 链接肝素的表皮生长因子样生长因子（HB-EGF）在胆脂瘤的发生和侵袭中起重要作用。本研究可能有助于了解胆脂瘤发病机理的分子机制, 使HB-EGF成为胆脂瘤药物干预的有前景的目标。

目的 探测HB-EGF在获得性中耳胆脂瘤手术标本中的表征, 并分析其作为控制上皮角化细胞过度增殖的功能性作用。

方法 本研究招录了34例接受中耳胆脂瘤手术治疗的患者。通过实时定量逆转录聚合酶链反应（RT-qPCR）、免疫组织化学染色和免疫印迹, 研究了中耳胆脂瘤组织和正常角膜上皮组织中HB-EGF的mRNA和蛋白质表征。还分析了骨吸收程度和HB-EGF表征之间的相关性。

结果 平均而言, 与正常的后角膜皮肤相比, 胆脂瘤上皮中HB-EGF 的mRNA表征, 根据RT-qPCR, 显著升高2.41倍, 根据免疫印迹显示HB-EGF蛋白质显著上调2.32倍。在胆脂瘤上皮的底层和上底层中观察到的阳性HB-EGF免疫染色明显强于正常的后角膜皮肤。同时, 发现HB-EGF蛋白表征与骨吸收程度之间存在明显的正相关性。

Keywords:

• Cholesteatoma
• HB-EGF
• bone resorption
• etiopathogenesis

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing the paper.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Grant number 81400457].