Abstract: Objective  To investigate the expression profile of chromosome 6 open reading frame 58/liver-enriched gene 1（C6orf58/LEG1） in chronic rhinosinusitis with nasal polyps (CRSwNP) tissues and explore its potential clinical significance. Methods  Four CRSwNP-related transcriptomic datasets (GSE136825, GSE36830, GSE72713, and GSE23552) were downloaded from the gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using R software with criteria of |log2 FC| ≥ 1 and adjusted P < 0.05, and the intersecting DEGs across all four datasets were determined. Nasal polyp tissues from 44 CRSwNP patients and nasal mucosa from 21 healthy controls were collected, and real-time quantitative reverse transcription polymerase chain reaction（RT-qPCR） was performed to detect C6orf58 mRNA expression. Publicly available single-cell RNA sequencing data were analyzed by uniform manifold approximation and projection（UMAP） clustering to define the cell-type-specific localization of C6orf58 and compare its expression between the two groups. Additionally, 4D label-free quantitative proteomics was performed on nasal polyp tissues from 3 CRSwNP patients and nasal mucosa from 3 healthy controls to validate LEG1 protein expression. Results  Bioinformatic analysis revealed that C6orf58 exhibited the most pronounced and consistent downregulation across all four GEO datasets. RT-qPCR confirmed that C6orf58 mRNA expression was significantly lower in CRSwNP tissues than that in healthy controls (P<0.01). Single-cell RNA sequencing analysis demonstrated that C6orf58 was predominantly enriched in glandular cells,  where its expression was significantly downregulated in  CRSwNP patients compared to healthy controls. No significant inter-group differences were observed in other cell types. Proteomic analysis further corroborated that LEG1 protein levels were significantly decreased in CRSwNP tissues, aligning with findings at the gene and mRNA levels. Conclusion  Reduced C6orf58/LEG1 expression in CRSwNP nasal polyps, particularly in glandular cells, points to a possible role in disease pathogenesis linked to glandular secretory dysfunction. It may represent a candidate biomarker meriting further study.

Key words: chronic rhinosinusitis with nasal polyps, chromosome 6 open reading frame 58, liver-enriched gene 1, glandular cells, single-cell sequencing, proteomics, differential expression