巨噬细胞表达基因在中耳胆脂瘤病理过程中的作用

目的：分析中耳胆脂瘤巨噬细胞的基因表达谱变化，基于差异基因探讨中耳胆脂瘤发生的分子机制。方法：选取2018年1月至12月在温州医科大学附属第一医院耳鼻咽喉科接受手术的53例慢性化脓性中耳炎患者，术中分别切取中耳胆脂瘤基质周围组织和非胆脂瘤中耳肉芽组织。随机选择3例胆脂瘤患者设为试验组，3例非胆脂瘤患者设为对照组，分析两组标本中巨噬细胞的基因表达谱差异，对差异基因进行GO和KEGG功能富集分析，再对排名靠前的差异基因进行关键基因分析。结果：在胆脂瘤巨噬细胞中，共筛选出124个上调基因，主要富集于炎症和免疫相关的信号转导通路。与细胞增殖和骨质破坏相关的角蛋白-13、MMPs等差异基因的表达发生了显著上调。结论：巨噬细胞的差异基因参与了炎症和免疫反应的多条信号通路；角蛋白-13、MMPs是影响细胞增殖和骨质破坏的关键基因，在中耳胆脂瘤的发生发展中可能起着重要作用。

The role of macrophages’ gene expression in the pathology of middle ear cholesteatoma

Objective: To analyze gene expression profiles of macrophages in middle ear and explore the molecular mechanism in the progression of middle ear cholesteatoma based on differential genes. Methods:Cholesteatoma perimatrix or granulation tissue was collected from 53 patients with middle ear cholesteatoma or chronic otitis media, who underwent mastoidectomy in ENT department from January 2018 to December 2018.Three patients with cholesteatoma were selected randomly as an experimental group and three patients without cholesteatoma as a control group. Gene expression profiles of two groups were compared and the underlying function of differentially expressed genes predicted by GO and KEGG enrichment analysis. The underlying trend of top genes was identified by key genetic analysis. Results: The current study showed that 124 out of 7 060 genes were significantly up-regulated (P<0.05) when compared with the patients without cholesteatoma. Gene enrichment analysis showed that these altered genes were involved in multiple signaling pathways associated with inflammatory and immune response. Keratin-13 and MMPs genes that affected the abnormal proliferation and bone destruction were significantly up-regulated in cholesteatoma. Conclusion: Our results suggest that these differential genes of macrophages are involved in multiple signaling pathways associated with inflammation and immunity. Keratin-13 and MMPs are key genes that affect cellular proliferation and bone destruction and may play a critical role in the progression of cholesteatoma.