Inflammation- and stress-related feature screening in recurrent respiratory papillomatosis: A seven-donor single-cell reanalysis with an external laryngeal squamous cell carcinoma transcriptomic context.

BACKGROUND: Recurrent respiratory papillomatosis (RRP) is an HPV-associated airway disease with incompletely defined inflammatory and tissue-remodeling programs. METHODS: All seven public 10x matrices in GSE261589 (four RRP and three HC donors) were reanalysed. After uniform quality control and unsupervised clustering, raw counts were aggregated by donor within coarse cellular strata. edgeR quasi-likelihood models and Benjamini-Hochberg correction were used to screen inflammation-, stress-, innate-defense-, chemokine-, and remodeling-related genes. RESULTS: A total of 64,044 cells passed quality control and formed 30 Leiden clusters. Donor composition and embedding structure were documented across the integrated dataset. FN1 in the myeloid stratum was the only transcript passing the within-stratum FDR threshold (log2 fold change 6.91, FDR 0.027), while DEFB4A, CXCL3, CXCL8, CXCL1, CXCL2, and SERPINE1 formed a prioritized candidate set. External paired LSCC analyses showed higher tumor expression of the CXCL1/CXCL2 co-annotated transcript cluster, CXCL8, and SERPINE1 and identified coordinated matrix-remodeling and squamous epithelial tumor-associated features. CONCLUSION: The seven-donor analysis provides a donor-aware single-cell framework for inflammatory and remodeling feature prioritization in RRP. The integrated framework additionally provides a malignant-laryngeal transcriptomic context for inflammatory, chemokine, and extracellular-matrix remodeling features.