CTSS as a novel biomarker for tissue remodeling in CRSwNP: insights from multi-omics research
1Department of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China;Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China;Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, P.R. China;Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, P.R. China.
Background:
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a refractory, relapsing upper airway inflammatory disorder cha-racterized by prominent tissue remodeling. Current therapeutic options remain suboptimal. We aimed to identify novel potential targets and biomarkers using integrative multi-omics.
Methodology:
We performed Mendelian randomization (MR) analyses integrating blood expression quantitative trait loci (eQTL) from eQTLGen and plasma protein quantitative trait loci (pQTL) from deCODE with nasal polyps (NP) genome-wide association study data from 8,496 NP patients and 371,520 controls. Significant targets underwent validation via bulk/single-cell RNA sequen-cing, immunohistochemistry, and immunofluorescence.
Results:
MR analyses identified 6 targets causally linked to NP risk in both eQTL and pQTL analyses. Therein, cathepsin S (CTSS) increased the risk of NP, exclusively demonstrating colocalization with NP and exhibiting significant upregulation in NP tissue. Single-cell data showed CTSS mainly express in monocyte/macrophages, and CTSS-high subsets enriched in CRSwNP vs. Control. Immunohistochemistry and immunofluorescence further confirmed high CTSS expression in NP. Moreover, CTSS expression cor-related with tissue remodeling pathways and associated with CRSwNP clinical severity.
Conclusions:
CTSS may contribute to the pathogenesis of CRSwNP by modulating tissue remodeling. CTSS is a noval biomarker for CRSwNP.
Insights
Cathepsin S (CTSS) is a novel biomarker for chronic rhinosinusitis with nasal polyps (CRSwNP). CTSS plays a role in CRSwNP pathogenesis by influencing tissue remodeling and is upregulated in nasal polyps.
Area of Science:
- Genetics
- Immunology
- Pathology
Background:
- Chronic rhinosinusitis with nasal polyps (CRSwNP) is a challenging inflammatory condition with significant tissue remodeling.
- Current treatments for CRSwNP are often suboptimal, necessitating the search for new therapeutic targets and biomarkers.
Purpose of the Study:
- To identify novel molecular targets and biomarkers for CRSwNP using an integrative multi-omics approach.
- To investigate the causal relationship between genetic variations and CRSwNP risk.
Main Methods:
- Mendelian randomization (MR) analyses integrating eQTL and pQTL data with genome-wide association study data for nasal polyps (NP).
- Validation of identified targets through bulk/single-cell RNA sequencing, immunohistochemistry, and immunofluorescence.
Main Results:
- MR analyses identified 6 potential targets causally linked to NP risk.
- Cathepsin S (CTSS) was identified as a key target, showing increased NP risk, colocalization with NP, and significant upregulation in NP tissue.
- CTSS is primarily expressed in monocytes/macrophages, with CTSS-high subsets enriched in CRSwNP patients, and its expression correlates with tissue remodeling and clinical severity.
Conclusions:
- CTSS may contribute to CRSwNP pathogenesis by modulating tissue remodeling processes.
- CTSS represents a novel biomarker for CRSwNP, offering potential for improved diagnostics or therapeutics.