Chronic rhinosinusitis with nasal polyps (CRSwNP) presents a significant clinical challenge due to structural tissue changes and high recurrence rates. Identifying specific molecular targets remains essential for improving patient outcomes. A pioneering multi-omics study has recently identified Cathepsin S in CRSwNP as a novel biomarker for tissue remodeling. By integrating large-scale genetic and proteomic data, the research team found that Cathepsin S (CTSS) increases the risk of developing nasal polyps.

The Role of Cathepsin S in CRSwNP Pathogenesis

Mendelian randomization analyses demonstrated that high CTSS levels directly link to an increased risk of nasal polyps. This specific protease primarily localizes within monocyte and macrophage subsets in the upper airway. Furthermore, single-cell transcriptomics revealed that these CTSS-high immune cells are significantly more abundant in diseased tissues. Consequently, these findings suggest that macrophages drive local inflammation through increased protease activity.

Multi-Omics Insights: Cathepsin S in CRSwNP and Tissue Remodeling

The research team utilized immunohistochemistry to confirm high CTSS expression within the polyps themselves. They discovered that CTSS levels correlate strongly with various tissue remodeling pathways. Moreover, these molecular signatures associate with the clinical severity of CRSwNP in patients. Therefore, CTSS represents both a diagnostic indicator and a potential target for future therapeutic interventions.

What is Cathepsin S in CRSwNP?

Cathepsin S (CTSS) is a cysteine protease that researchers have identified as a key driver of tissue remodeling and a causal risk factor for nasal polyps.

How do macrophages relate to CTSS levels?

Single-cell data shows that CTSS expression occurs primarily in monocytes and macrophages, which are more prevalent in the nasal tissues of affected patients.

Can CTSS predict disease severity?

Yes, because higher expression levels of this biomarker correlate significantly with increased clinical severity and tissue structural changes in CRSwNP.

Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

1. Li C et al. CTSS as a novel biomarker for tissue remodeling in CRSwNP: insights from multi-omics research. Rhinology. 2026 May 19. doi: 10.4193/Rhin25.504. PMID: 42153360.


2. London NR Jr, Ramanathan M Jr. Biomarkers in Chronic Rhinosinusitis with Nasal Polyps. Front Cell Dev Biol. 2021;9:691234.


3. Hwang JW, et al. Emerging Role of Proteases in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps. Front Med. 2022;9:875156.