Potential biomarkers in peripheral blood mononuclear cells of patients with sporadic Ménière's disease based on proteomics

Acta Otolaryngol. 2023 Aug;143(8):636-646. doi: 10.1080/00016489.2023.2241517. Epub 2023 Aug 21.

Abstract

Background: Ménière's disease (MD) mainly refers to the endolymphatic hydrops in membranous labyrinth of the inner ear. Application of the mass spectrometry-based proteomics techniques has not been applied in the field of MD.

Objectives: To search for potential differential proteins to identify the disease biomarkers and reveal disease bioinformatics-related mechanisms through applying protein technology to analyze the expression changes of peripheral blood mononuclear cells (PBMCs) in sporadic MD patients.

Material and methods: 15 MD patients and 15 healthy individuals were enrolled. PBMCs from them were extracted, and their protein expression was identified and compared by LC-MS/MS and spectra analysis.

Results: There was significant difference in protein expression between MD patients and the control group. GO and KEGG analysis showed that endocytosis was involved in MD patients. Western blot results of CHMP1A and MMP9 protein showed that the expression of CHMP1A was higher in the MD group than that in the control group, while MMP9 was down-regulated. Immunohistochemistry confirmed that CHMP1A and MMP9 were expressed in the endolymphatic sacs of MD patients and in the inner ear of adult mice.

Conclusions and significance: Endocytosis may be involved in the pathogenesis of sporadic MD, furthermore CHMP1A, VPS4A, FCN3 and MMP9 could be considered as potential biomarkers.

Keywords: ESCRT; Ménière’s disease; bioinformatics; endocytosis; proteomics.

Plain language summary

背景:梅尼埃病(MD)主要是指内耳耳膜迷路中的内淋巴积液。 基于质谱的蛋白质组学技术尚未在MD治疗上得到应用。目的:通过应用蛋白质技术分析散发性MD患者外周血单核细胞(PBMcs)的表达变化, 寻找潜在的分异性蛋白来识别该病生物标志物, 揭示该病生物信息学相关机制。材料和方法:纳入 15 名 MD 患者和 15 名健康人。 提取PBMcs, 通过lc-Ms/Ms和光谱分析鉴定并比较其蛋白表达。结果:MD患者与对照组的蛋白表达存在显著差异。 GO和KeGG分析表明, MD患者具有内吞作用。 chMP1a和MMP9蛋白的蛋白质印迹结果显示, MD组chMP1a的表达高于对照组, 而MMP9表达下降。 免疫组织化学证实, chMP1a和MMP9在MD患者的内淋巴囊和成年小鼠的内耳中有表达。结论及意义:内吞作用可能参与散发性MD的发病机制, chMP1a、VPs4a、FcN3和MMP9可作为潜在的生物标志物。.

MeSH terms

  • Animals
  • Biomarkers
  • Chromatography, Liquid
  • Endolymphatic Sac*
  • Leukocytes, Mononuclear
  • Matrix Metalloproteinase 9
  • Meniere Disease*
  • Mice
  • Proteomics
  • Tandem Mass Spectrometry

Substances

  • Matrix Metalloproteinase 9
  • Biomarkers