MicroRNA expression profiles in sinonasal biopsies to support diagnosis of granulomatosis with polyangiitis

Živanović, Milanka (author), Hočevar, Alojzija (author), Zidar, Nina (author), Volavšek, Metka (author), Bolha, Luka (author)

Objectives: To identify aberrantly expressed microRNAs (miRNAs) in sinonasal tissue biopsies of patients with granulomatosis with polyangiitis (GPA), associate their expression profiles to sinonasal histopathology, and assess their differential expression between subgroups of clinically proven GPA patients, healthy controls and patients exhibiting inflammation of other etiology. Methods: We included formalin-fixed, paraffin-embedded biopsy tissue samples of sinonasal mucosa from 37 patients with clinically proven GPA, 15 patients with inflammation of other etiology and 14 control patients with normal histology. Of the included GPA patients, 20 patients had characteristic GPA-related histological features, while 17 patients displayed non-specific GPA histopathology in their sinonasal biopsy. Assessment of histological parameters was performed using histopathological techniques, and analysis of miRNA expression with miRCURY LNA miRNA miRNome Human PCR Panels and quantitative real-time PCR. Results: We determined expression of 306 miRNAs in sinonasal biopsy samples, which displayed different extent of dysregulation between individual patient groups. Based on their potential to discriminate between the controls, non-GPA and GPA patient subgroups, dysregulation of 11 miRNAs was further assessed, of which miR-1-3p/-21-3p/-93-5p/-155-5p/-1248/-31-3p/-182-5p/-183-5p and let-7b-5p held the potential to stratify patients based on their sinonasal tissue miRNA profile. Notably, several of these miRNAs were associated with the presence of granulomas, vasculitis and necrosis in sinonasal biopsies of GPA patients. Conclusion: Our study identifies novel miRNAs putatively implicated in the pathogenesis of GPA, and highlights dysregulated miRNAs as supporting biomarkers in establishing GPA diagnosis, particularly in the early phases of the disease, or in patients with atypical GPA presentation.

• Language: English
• Keywords: granulomatosis with polyangiitis, sinonasal tissue, microRNA, inflammation, biomarker
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 14 str.
• Numbering: Vol. 6, art. 1579750
• PID: 20.500.12556/RUL-176593
• UDC: 616-002
• ISSN on article: 1664-3224
• DOI: 10.3389/fimmu.2025.1579750
• COBISS.SI-ID: 234656003
• Publication date in RUL: 24.12.2025

Record is a part of a journal

• Title: Frontiers in immunology
• Shortened title: Front. immunol.
• Publisher: Frontiers Media
• ISSN: 1664-3224
• COBISS.SI-ID: 30774233

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: granulomatoza s poliangiitisom, sinonazalno tkivo, mikroRNA, vnetje, biološki označevalec

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P3-0054
• Name: Patologija in molekularna genetika